Tipo de doença mitocondrial caracterizada por macrocefalia (cabeça grande) com leucodistrofia progressiva, encefalopatia, cardiomiopatia hipertrófica, miopatia, doença hepática, síndrome de Leigh, neuropatia óptica hereditária de Leber e algumas formas de doença de Parkinson. A doença é causada por mutações em qualquer um dos muitos genes e o padrão de herança depende do gene responsável.
Introdução
O que você precisa saber de cara
Tipo de doença mitocondrial caracterizada por macrocefalia (cabeça grande) com leucodistrofia progressiva, encefalopatia, cardiomiopatia hipertrófica, miopatia, doença hepática, síndrome de Leigh, neuropatia óptica hereditária de Leber e algumas formas de doença de Parkinson. A doença é causada por mutações em qualquer um dos muitos genes e o padrão de herança depende do gene responsável.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 107 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 264 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
41 genes identificados com associação a esta condição. Padrão de herança: Autosomal recessive, Mitochondrial inheritance, X-linked dominant.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:1959619). Essential for the catalytic activity and assembly of complex I (PubMed:1959619, PubMed:26929434)
Mitochondrion inner membrane
Leber hereditary optic neuropathy
A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 23
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN23 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membraneMitochondrion intermembrane space
Mitochondrial complex I deficiency, nuclear type 39
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN39 is an autosomal recessive form characterized by intrauterine growth retardation, anemia, and postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I defect with a fatal outcome.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 13
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN13 transmission pattern is consistent with autosomal recessive inheritance.
Mitochondrial protein enriched in neurons that acts as a regulator of mitochondrial respiration (By similarity). Associates with the ATP synthase complex and facilitates ATP synthesis (By similarity). May be a chaperone protein involved in the turnover of the subunits of mitochondrial complex I N-module. It facilitates the degradation of N-module subunits damaged by oxidative stress, and contributes to complex I functional efficiency (PubMed:33465056)
Mitochondrion inner membrane
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis but required for the complex assembly. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 36
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN36 is characterized by global developmental delay, hypotonia, and failure to thrive apparent from infancy or early childhood. Affected individuals usually do not acquire ambulation, show progressive spasticity, and have impaired intellectual development with absent speech. MC1DN36 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 32
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN32 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis (PubMed:27626371). Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (PubMed:27626371). Involved in the interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This apoptotic activity is inhibited by interaction with viral IRF1. Preve
Mitochondrion inner membraneNucleus
Hurthle cell thyroid carcinoma
A rare type of thyroid cancer accounting for only about 3-10% of all differentiated thyroid cancers. These neoplasms are considered a variant of follicular carcinoma of the thyroid and are referred to as follicular carcinoma, oxyphilic type.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Required for proper complex I assembly (PubMed:28671271). Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion matrix
Mitochondrial complex I deficiency, nuclear type 26
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN26 transmission pattern is consistent with autosomal recessive inheritance.
Methionyl-tRNA formyltransferase that formylates methionyl-tRNA in mitochondria and is crucial for translation initiation
Mitochondrion
Combined oxidative phosphorylation deficiency 15
An autosomal recessive, mitochondrial, neurologic disorder characterized by features of Leigh syndrome and combined oxidative phosphorylation deficiency. Clinical features include mild global developmental delay, white matter abnormalities, ataxia, incoordination, speech and reading difficulties, T2-weighted hyperintensities in the basal ganglia, corpus callosum, and brainstem.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion matrix
Mitochondrial complex I deficiency, nuclear type 22
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN22 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis (PubMed:27626371, PubMed:32385911, PubMed:33153867). Complex I functions in the transfer of electrons from NADH to the respiratory chain (PubMed:27626371). The immediate electron acceptor for the enzyme is believed to be ubiquinone (PubMed:27626371)
Mitochondrion inner membraneMitochondrion intermembrane spaceMitochondrion
Mitochondrial complex I deficiency, nuclear type 37
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN37 features include developmental delay, cerebral atrophy, epilepsy, growth retardation, congenital myopathy with disproportion of fibers, and severely decreased activity of complex I. MC1DN37 transmission pattern is consistent with autosomal recessive inheritance.
Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) at early stages. May play a role in the biogenesis of complex I subunit MT-ND1
Mitochondrion inner membraneCytoplasmNucleus
Mitochondrial complex I deficiency, nuclear type 17
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN17 transmission pattern is consistent with autosomal recessive inheritance.
Arginine hydroxylase that mediates hydroxylation of 'Arg-111' of NDUFS7 and is involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) at early stages (PubMed:18940309, PubMed:27226634). May also have methyltransferase activity (Probable)
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 16
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN16 transmission pattern is consistent with autosomal recessive inheritance.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:28844695). Part of the peripheral arm of the enzyme, where the electrons from NADH are accepted by flavin mononucleotide (FMN) and then passed along a chain of iron-sulfur clusters by electron tunnelling to the final acceptor ubiquinone (PubMed:28844695). Contains FMN, which is the i
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 4
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN4 transmission pattern is consistent with autosomal recessive inheritance.
Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) (PubMed:27499296). Required to stabilize NDUFAF5 (PubMed:27499296)
Mitochondrion
Mitochondrial complex I deficiency, nuclear type 34
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN34 transmission pattern is consistent with autosomal recessive inheritance.
Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) (PubMed:20858599, PubMed:25678554). Involved in mid-late stages of complex I assembly (PubMed:25678554)
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 19
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN19 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 12
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.
Acts as a molecular chaperone for mitochondrial complex I assembly (PubMed:16200211, PubMed:19384974). Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (PubMed:16200211, PubMed:27626371). Is involved in the initial steps of cilia formation, including removal of CP110 from the mother centrioles, docking of membrane vesicles to the mother centrioles, and establishment of the transition z
Mitochondrion
Mitochondrial complex I deficiency, nuclear type 10
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN10 transmission pattern is consistent with autosomal recessive inheritance.
Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Participates in constructing the membrane arm of complex I
Mitochondrion membrane
Mitochondrial complex I deficiency, nuclear type 31
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN31 transmission pattern is consistent with autosomal recessive inheritance.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:16996290). Essential for the catalytic activity and assembly of complex I (PubMed:16996290)
Mitochondrion inner membrane
Leber hereditary optic neuropathy
A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
Iron-sulfur cluster transfer protein involved in the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) (PubMed:19752196). May deliver one or more Fe-S clusters to complex I subunits (PubMed:19752196)
Mitochondrion
Mitochondrial complex I deficiency, nuclear type 21
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN21 transmission pattern is consistent with autosomal recessive inheritance.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:22036843, PubMed:28031252, PubMed:30922174). Essential for the catalytic activity of complex I (PubMed:22036843, PubMed:30922174). Essential for the assembly of complex I (By similarity). Redox-sensitive, critical component of the oxygen-sensing pathway in the pulmonary vasculature w
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 6
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN6 transmission pattern is consistent with autosomal recessive inheritance.
As part of the MCIA complex, involved in the assembly of the mitochondrial complex I (PubMed:27374773, PubMed:27374774, PubMed:32320651). Participates in constructing the membrane arm of complex I (PubMed:24191001)
Mitochondrion membrane
Mitochondrial complex I deficiency, nuclear type 29
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN29 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Linear skin defects with multiple congenital anomalies 3
A disorder characterized by dermal, ocular, neurological and cardiac abnormalities. LSDMCA3 clinical features include linear skin defects on face and neck at birth, lacrimal duct atresia, myopia, nystagmus, strabismus, cardiomyopathy, axial hypotonia, seizures, corpus callosum agenesis, and dilation of lateral ventricles.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 9
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN9 transmission pattern is consistent with autosomal recessive inheritance.
Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) (PubMed:18179882, PubMed:28853723). May be involved in cell proliferation and survival of hormone-dependent tumor cells. May be a regulator of breast tumor cell invasion
MitochondrionMembrane
Mitochondrial complex I deficiency, nuclear type 15
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN15 transmission pattern is consistent with autosomal recessive inheritance.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:17275378). Essential for the catalytic activity of complex I (PubMed:17275378)
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 3
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN3 transmission pattern is consistent with autosomal recessive inheritance.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:25118196). Essential for the catalytic activity of complex I (PubMed:25118196)
Mitochondrion inner membrane
Leigh syndrome
An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.
Accessory subunit that is involved in the functional assembly of the mitochondrial respiratory chain complex I. Complex I has an NADH dehydrogenase activity with ubiquinone as an immediate electron acceptor and mediates the transfer of electrons from NADH to the respiratory chain
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 35
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN35 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 14
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN14 transmission pattern is consistent with autosomal recessive inheritance.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:30879903, PubMed:31557978). Essential for catalysing the entry and efficient transfer of electrons within complex I (PubMed:31557978). Plays a key role in the assembly and stability of complex I and participates in the association of complex I with ubiquinol-cytochrome reductase comp
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 5
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN5 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 24
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN24 transmission pattern is consistent with autosomal recessive inheritance.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:14729820, PubMed:30140060). Essential for the catalytic activity and assembly of complex I (PubMed:14729820, PubMed:24028823, PubMed:30140060)
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 8
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN8 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 25
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN25 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 1
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:22499348). Essential for the catalytic activity and assembly of complex I (PubMed:22499348)
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 2
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN2 inheritance is autosomal recessive.
As part of the MCIA complex, involved in the assembly of the mitochondrial complex I
MitochondrionMitochondrion matrix
Mitochondrial complex I deficiency, nuclear type 11
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN11 transmission pattern is consistent with autosomal recessive inheritance.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in catalysis. Required for proper complex I assembly (PubMed:30245030). Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 33
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN33 transmission pattern is consistent with autosomal recessive inheritance.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (Probable). Parts of the peripheral arm of the enzyme, where the electrons from NADH are accepted by flavin mononucleotide (FMN) and then passed along a chain of iron-sulfur clusters by electron tunnelling to the final acceptor ubiquinone (Probable). Contains one iron-sulfur cluster (Probabl
Mitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 7
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN7 transmission pattern is consistent with autosomal recessive inheritance.
Essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I)
NucleusMitochondrion inner membrane
Mitochondrial complex I deficiency, nuclear type 18
A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN18 transmission pattern is consistent with autosomal recessive inheritance.
Variantes genéticas (ClinVar)
83 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
8 vias biológicas associadas aos genes desta condição.
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Publicações mais relevantes
Biallelic NDUFA13 variants lead to a neurodevelopmental phenotype with gradual neurological impairment.
Biallelic variants in NADH (nicotinamide adenine dinucleotide (NAD) + hydrogen (H))-ubiquinone oxidoreductase 1 alpha subcomplex 13 have been linked to mitochondrial complex I deficiency, nuclear type 28, based on three affected individuals from two families. With only two families reported, the clinical and molecular spectrum of NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13-related diseases remains unclear. We report 10 additional affected individuals from nine independent families, identifying four missense variants (including recurrent c.170G > A) and three ultra-rare or novel predicted loss-of-function biallelic variants. Updated clinical-radiological data from previously reported families and a literature review compiling clinical features of all reported patients with isolated complex I deficiency caused by 43 genes encoding complex I subunits and assembly factors are also provided. Our cohort (mean age 7.8 ± 5.4 years; range 2.5-18) predominantly presented a moderate-to-severe neurodevelopmental syndrome with oculomotor abnormalities (84%), spasticity/hypertonia (83%), hypotonia (69%), cerebellar ataxia (66%), movement disorders (58%) and epilepsy (46%). Neuroimaging revealed bilateral symmetric T2 hyperintense substantia nigra lesions (91.6%) and optic nerve atrophy (66.6%). Protein modeling suggests missense variants destabilize a critical junction between the hydrophilic and membrane arms of complex I. Fibroblasts from two patients showed reduced complex I activity and compensatory complex IV activity increase. This study characterizes NADH-ubiquinone oxidoreductase 1 alpha subcomplex 13-related disease in 13 individuals, highlighting genotype-phenotype correlations.
Tissue-Specific Regulation of Fatty Acid Metabolism in a Mouse Model of Isolated Complex I Deficiency.
Isolated complex I deficiency (ICD) is commonly associated with mitochondrial diseases and closely mimics subacute necrotising encephalomyelopathy. This disorder is characterised by metabolic perturbations that affect energy metabolism pathways, including fatty acid metabolism. Here, we examined the tissue-specific changes in fatty acid metabolism in the Ndufs4 KO mice by employing mass-spectrometry-based proteomics as a hypothesis-generating approach. We investigated proteomic changes in six tissues, including brain regions (brainstem, cerebellum, olfactory bulb), heart, kidney and liver, focusing on proteins involved in fatty acid metabolism. Although it is expected that most tissues, except for the brain, will utilise fatty acids as alternative energy sources when oxidative phosphorylation (OXPHOS) is deficient, our data revealed a more complex response. In the liver, fatty acid consumption (oxidation) was favoured as expected, but in the heart, fatty acid synthesis was favoured. In the kidney, proteins involved in almost all fatty acid metabolic processes (oxidation and synthesis) were downregulated. Our data demonstrate that metabolic adaptations in fatty acid metabolism to ICD were tissue-specific and often in opposing directions. Understanding the differential adaptations across tissues could inform future treatment targets for mitochondrial disorders.
Ndufs4 knockout mice with isolated complex I deficiency engage a futile adaptive brain response.
Paediatric Leigh syndrome (LS) is an early-onset and fatal neurodegenerative disorder lacking treatment options. LS is frequently caused by mutations in the NDUFS4 gene, encoding an accessory subunit of mitochondrial complex I (CI), the first complex of the oxidative phosphorylation (OXPHOS) system. Whole-body Ndufs4 knockout (KO) mice (WB-KO mice) are widely used to study isolated CI deficiency, LS pathology and interventions. These animals develop a brain-specific phenotype via an incompletely understood pathomechanism. Here we performed a quantitative analysis of the sub-brain proteome in six-weeks old WB-KO mice vs. wildtype (WT) mice. Brain regions comprised of a brain slice (BrSl), cerebellum (CB), cerebral cortex (CC), hippocampus (HC), inferior colliculus (IC), and superior colliculus (SC). Proteome analysis demonstrated similarities between CC/HC, and between IC/SC, whereas BrSl and CB differed from these two groups and each other. All brain regions displayed greatly reduced levels of two CI structural subunits (NDUFS4, NDUFA12) and an increased level of the CI assembly factor NDUFAF2. The level of CI-Q module subunits was significantly more reduced in IC/SC than in BrSl/CB/CC/HC, whereas other OXPHOS complex levels were not reduced. Gene ontology and pathway analysis demonstrated specific and common proteome changes between brain regions. Across brain regions, upregulation of cold-shock-associated proteins, mitochondrial fatty acid (FA) oxidation and synthesis (mtFAS) were the most prominent. FA-related pathways were predominantly upregulated in CB and HC. Based upon these results, we argue that stimulation of these pathways is futile and pro-pathological and discuss alternative strategies for therapeutic intervention in LS. SIGNIFICANCE: The Ndufs4 knockout mouse model is currently the most relevant and most widely used animal model to study the brain-linked pathophysiology of human Leigh Syndrome (LS) and intervention strategies. We demonstrate that the Ndufs4 knockout brain engages futile and pro-pathological responses. These responses explain both negative and positive outcomes of intervention studies in Leigh Syndrome mice and patients, thereby guiding novel intervention opportunities.
A Novel Mutation Associated with Neonatal Lethal Cardiomyopathy Leads to an Alternative Transcript Expression in the X-Linked Complex I NDUFB11 Gene.
We report a neonatal patient with hypertrophic cardiomyopathy (HCM), lactic acidosis and isolated complex I deficiency. Using a customized next-generation sequencing panel, we identified a novel hemizygous variant c.338G>A in the X-linked NDUFB11 gene that encodes the NADH: ubiquinone oxidoreductase subunit B11 of the mitochondrial respiratory chain (MRC) complex I (CI). Molecular and functional assays performed in the proband’s target tissues—skeletal and heart muscle—showed biochemical disturbances of the MRC, suggesting a pathogenic role for this variant. In silico analyses initially predicted an amino acid missense change p.(Arg113Lys) in the NDUFB11 CI subunit. However, we showed that the molecular effect of the c.338G>A variant, which is located at the last nucleotide of exon 2 of the NDUFB11 gene in the canonical ‘short’ transcript (sized 462 bp), instead causes a splicing defect triggering the up-regulation of the expression of an alternative ‘long’ transcript (sized 492 bp) that can also be detected in the control individuals. Our results support the hypothesis that the canonical ‘short’ transcript is required for the proper NDUFB11 protein synthesis, which is essential for optimal CI assembly and activity, whereas the longer alternative transcript seems to represent a non-functional, unprocessed splicing intermediate. Our results highlight the importance of characterizing the molecular effect of new variants in the affected patient’s tissues to demonstrate their pathogenicity and association with the clinical phenotypes.
Impact of the m.13513G>A Variant on the Functions of the OXPHOS System and Cell Retrograde Signaling.
Mitochondria are involved in many vital functions in living cells, including the synthesis of ATP by oxidative phosphorylation (OXPHOS) and regulation of nuclear gene expression through retrograde signaling. Leigh syndrome is a heterogeneous neurological disorder resulting from an isolated complex I deficiency that causes damage to mitochondrial energy production. The pathogenic mitochondrial DNA (mtDNA) variant m.13513G>A has been associated with Leigh syndrome. The present study investigated the effects of this mtDNA variant on the OXPHOS system and cell retrograde signaling. Transmitochondrial cytoplasmic hybrid (cybrid) cell lines harboring 50% and 70% of the m.13513G>A variant were generated and tested along with wild-type (WT) cells. The functionality of the OXPHOS system was evaluated by spectrophotometric assessment of enzyme activity and high-resolution respirometry. Nuclear gene expression was investigated by RNA sequencing and droplet digital PCR. Increasing levels of heteroplasmy were associated with reduced OXPHOS system complex I, IV, and I + III activities, and high-resolution respirometry also showed a complex I defect. Profound changes in transcription levels of nuclear genes were observed in the cell lines harboring the pathogenic mtDNA variant, indicating the physiological processes associated with defective mitochondria.
Publicações recentes
Tissue-Specific Regulation of Fatty Acid Metabolism in a Mouse Model of Isolated Complex I Deficiency.
Biallelic NDUFA13 variants lead to a neurodevelopmental phenotype with gradual neurological impairment.
Ndufs4 knockout mice with isolated complex I deficiency engage a futile adaptive brain response.
Impact of the m.13513G>A Variant on the Functions of the OXPHOS System and Cell Retrograde Signaling.
A Novel Mutation Associated with Neonatal Lethal Cardiomyopathy Leads to an Alternative Transcript Expression in the X-Linked Complex I NDUFB11 Gene.
📚 EuropePMC14 artigos no totalmostrando 33
Tissue-Specific Regulation of Fatty Acid Metabolism in a Mouse Model of Isolated Complex I Deficiency.
ProteomicsBiallelic NDUFA13 variants lead to a neurodevelopmental phenotype with gradual neurological impairment.
Brain communicationsNdufs4 knockout mice with isolated complex I deficiency engage a futile adaptive brain response.
Biochimica et biophysica acta. Proteins and proteomicsImpact of the m.13513G>A Variant on the Functions of the OXPHOS System and Cell Retrograde Signaling.
Current issues in molecular biologyA Novel Mutation Associated with Neonatal Lethal Cardiomyopathy Leads to an Alternative Transcript Expression in the X-Linked Complex I NDUFB11 Gene.
International journal of molecular sciencesCase Report: Optic Atrophy and Nephropathy With m.13513G>A/MT-ND5 mtDNA Pathogenic Variant.
Frontiers in geneticsMesenchymal stem cells improve redox homeostasis and mitochondrial respiration in fibroblast cell lines with pathogenic MT-ND3 and MT-ND6 variants.
Stem cell research & therapyNdufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention.
Brain : a journal of neurologyGenome sequencing and RNA-seq analyses of mitochondrial complex I deficiency revealed Alu insertion-mediated deletion in NDUFV2.
Human mutationThe m.3890G>A/MT-ND1 mtDNA rare pathogenic variant: Expanding clinical and MRI phenotypes.
MitochondrionOptic atrophy-associated TMEM126A is an assembly factor for the ND4-module of mitochondrial complex I.
Proceedings of the National Academy of Sciences of the United States of AmericaSevere congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7.
Human mutationMultiomic analysis elucidates Complex I deficiency caused by a deep intronic variant in NDUFB10.
Human mutationNovel MT-ND Gene Variants Causing Adult-Onset Mitochondrial Disease and Isolated Complex I Deficiency.
Frontiers in geneticsA meta-analysis and systematic review of Leigh syndrome: clinical manifestations, respiratory chain enzyme complex deficiency, and gene mutations.
MedicinePathogenic Bi-allelic Mutations in NDUFAF8 Cause Leigh Syndrome with an Isolated Complex I Deficiency.
American journal of human geneticsDiverse phenotype in patients with complex I deficiency due to mutations in NDUFB11.
European journal of medical geneticsBi-allelic Mutations in NDUFA6 Establish Its Role in Early-Onset Isolated Mitochondrial Complex I Deficiency.
American journal of human geneticsClinical, biochemical, and genetic analysis of the mitochondrial respiratory chain complex I deficiency.
MedicineMammalian Mitochondrial Complex I Structure and Disease-Causing Mutations.
Trends in cell biologyLifetime exercise intolerance with lactic acidosis as key manifestation of novel compound heterozygous ACAD9 mutations causing complex I deficiency.
Neuromuscular disorders : NMDWidening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation.
JIMD reportsBenign mitochondrial myopathy with exercise intolerance in a large multigeneration family due to a homoplasmic m.3250T>C mutation in MTTL1.
European journal of neurologyPure myopathy with enlarged mitochondria associated to a new mutation in MTND2 gene.
Molecular genetics and metabolism reportsMutations in the accessory subunit NDUFB10 result in isolated complex I deficiency and illustrate the critical role of intermembrane space import for complex I holoenzyme assembly.
Human molecular geneticsDeep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism.
PloS oneMutations in Complex I Assembly Factor TMEM126B Result in Muscle Weakness and Isolated Complex I Deficiency.
American journal of human geneticsA recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype.
Journal of medical geneticsLeigh Syndrome in Childhood: Neurologic Progression and Functional Outcome.
Journal of clinical neurology (Seoul, Korea)High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood.
European journal of human genetics : EJHGDeficiency of respiratory chain complex I in Hashimoto thyroiditis.
MitochondrionIncreased mitochondrial ATP production capacity in brain of healthy mice and a mouse model of isolated complex I deficiency after isoflurane anesthesia.
Journal of inherited metabolic diseaseBroad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1.
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Biallelic NDUFA13 variants lead to a neurodevelopmental phenotype with gradual neurological impairment.
- Tissue-Specific Regulation of Fatty Acid Metabolism in a Mouse Model of Isolated Complex I Deficiency.
- Ndufs4 knockout mice with isolated complex I deficiency engage a futile adaptive brain response.
- A Novel Mutation Associated with Neonatal Lethal Cardiomyopathy Leads to an Alternative Transcript Expression in the X-Linked Complex I NDUFB11 Gene.
- Impact of the m.13513G>A Variant on the Functions of the OXPHOS System and Cell Retrograde Signaling.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:2609(Orphanet)
- MONDO:0100133(MONDO)
- GARD:3908(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q23542367(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
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