A Amaurose Congênita de Leber (ACL) é uma doença da retina (a parte do olho que capta a luz) que causa cegueira. Ela é diagnosticada quando as respostas a exames que medem a atividade elétrica da retina (como o eletroretinograma de Ganzfeld, ou ERG) estão muito abaixo do normal ou são praticamente inexistentes. A condição está associada a uma perda visual grave que surge já no primeiro ano de vida da criança.
Introdução
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A Amaurose Congênita de Leber (ACL) é uma doença da retina (a parte do olho que capta a luz) que causa cegueira. Ela é diagnosticada quando as respostas a exames que medem a atividade elétrica da retina (como o eletroretinograma de Ganzfeld, ou ERG) estão muito abaixo do normal ou são praticamente inexistentes. A condição está associada a uma perda visual grave que surge já no primeiro ano de vida da criança.
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 28 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 93 características clínicas mais associadas, ordenadas por frequência.
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
22 genes identificados com associação a esta condição. Padrão de herança: Autosomal dominant, Autosomal recessive.
Retinoids dehydrogenase/reductase with a clear preference for NADP. Displays high activity towards 9-cis, 11-cis and all-trans-retinal. Shows very weak activity towards 13-cis-retinol (PubMed:12226107, PubMed:15865448). Also exhibits activity, albeit with lower affinity than for retinaldehydes, towards lipid peroxidation products (C9 aldehydes) such as 4-hydroxynonenal and trans-2-nonenal (PubMed:15865448, PubMed:19686838). May play an important function in photoreceptor cells to detoxify 4-hydr
Endoplasmic reticulum membrane
Leber congenital amaurosis 13
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
May be important in protein trafficking and/or protein folding and stabilization
CytoplasmNucleus
Leber congenital amaurosis 4
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Involved in the maintenance of both rod and cone photoreceptor cells (By similarity). It is required for recruitment and proper localization of RPGRIP1 to the photoreceptor connecting cilium (CC), as well as photoreceptor-specific localization of proximal CC proteins at the distal CC (By similarity). Maintenance of protein localization at the photoreceptor-specific distal CC is essential for normal microtubule stability and to prevent photoreceptor degeneration (By similarity)
Cytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, cilium basal bodyCytoplasm, cytoskeletonCell projection, cilium, photoreceptor outer segment
Leber congenital amaurosis 3
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ13 has a very low single channel conductance, low sensitivity to
MembraneCell membrane
Snowflake vitreoretinal degeneration
Developmental and progressive hereditary eye disorder that affects multiple tissues within the eye. Diagnostic features of SVD include fibrillar degeneration of the vitreous humor, early-onset cataract, minute crystalline deposits in the neurosensory retina, and retinal detachment.
Involved in early and late steps in cilia formation. Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (PubMed:18694559). May play a role in early ciliogenesis in the disappearance of centriolar satellites and in the transition of primary ciliar vesicles (PCVs) to capped ciliary vesicles (CCVs). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1 (PubMed:24421332). Require
Cytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satelliteNucleusCell projection, ciliumCytoplasm, cytoskeleton, cilium basal bodyCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleCytoplasmic vesicle
Joubert syndrome 5
A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 5 shares the neurologic and neuroradiologic features of Joubert syndrome together with severe retinal dystrophy and/or progressive renal failure characterized by nephronophthisis.
Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors
Nucleus
Leber congenital amaurosis 7
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis
Cytoplasm, cytosolMembraneEndoplasmic reticulum membraneNucleus
Spondylometaphyseal dysplasia with cone-rod dystrophy
An autosomal recessive disorder characterized by postnatal growth deficiency resulting in profound short stature, rhizomelia with bowing of the lower extremities, platyspondyly with anterior vertebral protrusions, progressive metaphyseal irregularity and cupping with shortened tubular bones, and early-onset progressive visual impairment associated with a pigmentary maculopathy and electroretinographic evidence of cone-rod dysfunction.
Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters (PubMed:9920938). Retinyl esters are storage forms of vitamin A (Probable). LRAT plays a critical role in vision (Probable). It provides the all-trans retinyl ester substrates for the isomerohydrolase which processes the esters into 11-cis-retinol in the retinal pigment epithelium; due to a membrane-associated alcohol dehydrogenase, 11 cis-retinol is oxidized and conver
Endoplasmic reticulum membraneRough endoplasmic reticulumEndosome, multivesicular bodyCytoplasm, perinuclear region
Leber congenital amaurosis 14
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Catalyzes the synthesis of cyclic GMP (cGMP) in rods and cones of photoreceptors. Plays an essential role in phototransduction, by mediating cGMP replenishment (PubMed:15123990, PubMed:21928830, PubMed:26100624, PubMed:30319355, PubMed:9600905). May also participate in the trafficking of membrane-associated proteins to the photoreceptor outer segment membrane (By similarity)
Photoreceptor outer segment membraneEndoplasmic reticulum membrane
Leber congenital amaurosis 1
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Involved in ciliogenesis. The function in an early step in cilia formation depends on its association with CEP290/NPHP6 (PubMed:21565611, PubMed:23446637). Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2 and BBS5 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating CEP290/NPHP6 (PubMed:25552655)
Cytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole
Senior-Loken syndrome 5
A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.
Plays a role in photoreceptor morphogenesis in the retina (By similarity). May maintain cell polarization and adhesion (By similarity)
Apical cell membraneSecretedCell projection, cilium, photoreceptor outer segmentPhotoreceptor inner segment
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin
Cytoplasm, cytoskeletonCytoplasm, cytoskeleton, flagellum axoneme
Leber congenital amaurosis with early-onset deafness
An autosomal dominant disease characterized by severe retinal degeneration and sensorineural hearing loss. Symptoms occur within the first decade of life. Onset at birth is observed in some patients.
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors
CytoplasmNucleus
Retinitis pigmentosa 10
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
May function as scaffolding protein. Required for normal location of RPGR at the connecting cilium of photoreceptor cells. Required for normal disk morphogenesis and disk organization in the outer segment of photoreceptor cells and for survival of photoreceptor cells
Cell projection, cilium
Leber congenital amaurosis 6
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Catalyzes the deubiquitination of SPDL1 (PubMed:30258100). Plays a role in the repair of UV-induced DNA damage via deubiquitination of ERCC1, promoting its recruitment to DNA damage sites (PubMed:25538220). May be involved in the maintenance of photoreceptor function (PubMed:30573563). May play a role in normal retinal development (By similarity). Plays a role in cell migration (PubMed:30258100)
Photoreceptor inner segmentCytoplasmNucleus
Leber congenital amaurosis 19
A form of Leber congenital amaurosis, a severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. LCA19 is an autosomal recessive form characterized by reduced vision in early childhood and severely reduced responses of both rods and cones.
Plays a critical role in the regulation of enzymes involved in nucleotide cycle in photoreceptors (PubMed:21078983, PubMed:21928830, PubMed:27471269, PubMed:29515371, PubMed:30559291). Inhibits the basal catalytic activity and the GCAP-stimulated activity of GUCY2D and GUCY2F, two retinal guanylyl cyclases involved in the production of cGMP in photoreceptors (PubMed:21928830, PubMed:27471269, PubMed:29515371, PubMed:30559291). Involved in the transport of GUCY2D and GUCY2F to their target sites
Cell projection, cilium, photoreceptor outer segmentPhotoreceptor inner segmentEndosomeNucleusCytoplasmCytoplasm, perinuclear region
Leber congenital amaurosis 12
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs) (PubMed:20889716, PubMed:22503633). Plays a pivotal role in proper development and function of ciliated cells through its role in ciliogenesis and/or cilium maintenance (PubMed:22503633). Required for the development and maintenance of the outer segments of rod and cone photoreceptor cells. Plays a role in maintenance and the delivery of opsin to
Cytoplasm, cytoskeleton, cilium basal bodyCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCell projection, cilium
Short-rib thoracic dysplasia 9 with or without polydactyly
A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. SRTD9 is characterized by phalangeal cone-shaped epiphyses, chronic renal disease, nearly constant retinal dystrophy, and mild radiographic abnormality of the proximal femur. Occasional features include short stature, cerebellar ataxia, and hepatic fibrosis.
Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells (By similarity). Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4
CytoplasmCell membraneSecretedSynapse
Retinitis pigmentosa 14
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins. Catalyzes the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol which is further oxidized by 11-cis retinol dehydrogenase to 11-cis-retinal for use as visual chromophore (PubMed:16116091). Essential for the production of 11-cis retinal for both rod and cone photoreceptors (PubMed:17848510). Also capable of catalyzing the isomerizati
CytoplasmCell membraneMicrosome membrane
Leber congenital amaurosis 2
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Involved in intraflagellar protein (IFT) transport in photoreceptor cilia. Plays a role in the ciliary transport of photoreceptors outer segment proteins
Cytoplasm, cytoskeletonCytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, cilium basal bodyCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCell projection, cilium
Leber congenital amaurosis 5
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (PubMed:17402747). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency (PubMed:17402747). Can use triazofurin monophosphate (TrMP) as substrate (PubMed:17402747). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (PubMed:17402747). For the pyrophosphorolytic activity, prefers NAD(+) and NaAD as substrates and degrades NADH, ni
Nucleus
Leber congenital amaurosis 9
A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.
Growth factor that controls proliferation and cellular differentiation in the retina and bone formation. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal-ventral positional information in the retina and controls the formation of the retinotectal map (PubMed:23307924). Required for normal formation of bones and joints in the limbs, skull, digits and axial skeleton. Plays a key role in establishing boundaries between skeletal elements during development. Regu
Secreted
Klippel-Feil syndrome 1, autosomal dominant
A skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. Deafness is a feature in some cases and may be of sensorineural, conductive, or mixed type.
Medicamentos e terapias
Mecanismo: Retinoid isomerohydrolase exogenous gene
Mecanismo: Glucocorticoid receptor agonist
Mecanismo: Glucocorticoid receptor agonist
Mecanismo: CEP290 mRNA positive modulator
Variantes genéticas (ClinVar)
437 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 10,146 variantes classificadas pelo ClinVar.
Vias biológicas (Reactome)
42 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Amaurose congênita de Leber
Centros de Referência SUS
24 centros habilitados pelo SUS para Amaurose congênita de Leber
Centros para Amaurose congênita de Leber
Detalhes dos centros
Hospital Universitário Prof. Edgard Santos (HUPES)
R. Dr. Augusto Viana, s/n - Canela, Salvador - BA, 40110-060 · CNES 0003808
Serviço de Referência
Hospital Infantil Albert Sabin
R. Tertuliano Sales, 544 - Vila União, Fortaleza - CE, 60410-794 · CNES 2407876
Serviço de Referência
Hospital de Apoio de Brasília (HAB)
AENW 3 Lote A Setor Noroeste - Plano Piloto, Brasília - DF, 70684-831 · CNES 0010456
Serviço de Referência
Hospital Estadual Infantil e Maternidade Alzir Bernardino Alves (HIABA)
Av. Min. Salgado Filho, 918 - Soteco, Vila Velha - ES, 29106-010 · CNES 6631207
Serviço de Referência
Hospital das Clínicas da UFG
Rua 235 QD. 68 Lote Área, Nº 285, s/nº - Setor Leste Universitário, Goiânia - GO, 74605-050 · CNES 2338424
Serviço de Referência
Hospital Universitário da UFJF
R. Catulo Breviglieri, Bairro - s/n - Santa Catarina, Juiz de Fora - MG, 36036-110 · CNES 2297442
Atenção Especializada
Hospital das Clínicas da UFMG
Av. Prof. Alfredo Balena, 110 - Santa Efigênia, Belo Horizonte - MG, 30130-100 · CNES 2280167
Serviço de Referência
Hospital Universitário Julio Müller (HUJM)
R. Luis Philippe Pereira Leite, s/n - Alvorada, Cuiabá - MT, 78048-902 · CNES 2726092
Atenção Especializada
Hospital Universitário João de Barros Barreto
R. dos Mundurucus, 4487 - Guamá, Belém - PA, 66073-000 · CNES 2337878
Serviço de Referência
Hospital Universitário Lauro Wanderley (HULW)
R. Tabeliao Estanislau Eloy, 585 - Castelo Branco, João Pessoa - PB, 58050-585 · CNES 0002470
Atenção Especializada
Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)
R. dos Coelhos, 300 - Boa Vista, Recife - PE, 50070-902 · CNES 0000647
Serviço de Referência
Hospital Pequeno Príncipe
R. Des. Motta, 1070 - Água Verde, Curitiba - PR, 80250-060 · CNES 3143805
Serviço de Referência
Hospital Universitário Regional de Maringá (HUM)
Av. Mandacaru, 1590 - Parque das Laranjeiras, Maringá - PR, 87083-240 · CNES 2216108
Atenção Especializada
Hospital de Clínicas da UFPR
R. Gen. Carneiro, 181 - Alto da Glória, Curitiba - PR, 80060-900 · CNES 2364980
Serviço de Referência
Hospital Universitário Pedro Ernesto (HUPE-UERJ)
Blvd. 28 de Setembro, 77 - Vila Isabel, Rio de Janeiro - RJ, 20551-030 · CNES 2280221
Serviço de Referência
Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/Fiocruz)
Av. Rui Barbosa, 716 - Flamengo, Rio de Janeiro - RJ, 22250-020 · CNES 2269988
Serviço de Referência
Hospital São Lucas da PUCRS
Av. Ipiranga, 6690 - Jardim Botânico, Porto Alegre - RS, 90610-000 · CNES 2232928
Serviço de Referência
Hospital de Clínicas de Porto Alegre (HCPA)
Rua Ramiro Barcelos, 2350 Bloco A - Av. Protásio Alves, 211 - Bloco B e C - Santa Cecília, Porto Alegre - RS, 90035-903 · CNES 2237601
Serviço de Referência
Hospital Universitário da UFSC (HU-UFSC)
R. Profa. Maria Flora Pausewang - Trindade, Florianópolis - SC, 88036-800 · CNES 2560356
Serviço de Referência
Hospital das Clínicas da FMUSP
R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo - SP, 05403-010 · CNES 2077485
Serviço de Referência
Hospital de Base de São José do Rio Preto
Av. Brg. Faria Lima, 5544 - Vila Sao Jose, São José do Rio Preto - SP, 15090-000 · CNES 2079798
Atenção Especializada
Hospital de Clínicas da UNICAMP
R. Vital Brasil, 251 - Cidade Universitária, Campinas - SP, 13083-888 · CNES 2748223
Serviço de Referência
Hospital de Clínicas de Ribeirão Preto (HCRP-USP)
R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto - SP, 14015-010 · CNES 2082187
Serviço de Referência
UNIFESP / Hospital São Paulo
R. Napoleão de Barros, 715 - Vila Clementino, São Paulo - SP, 04024-002 · CNES 2688689
Serviço de Referência
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
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Mostrando amostra de 200 publicações de um total de 728
Establishment of an induced pluripotent stem cell line from a patient with Leber Congenital Amaurosis.
A human induced pluripotent stem cell (hiPSC) line BTHBIOi006-A was generated from peripheral blood mononuclear cells of a patient carrying RDH12 biallelic mutations via episomal reprogramming. The line exhibits a normal karyotype, expresses pluripotent markers, differentiates into three germ layers, and is mycoplasma-free, serving as a tool for retinal disease research.
Functional In Vitro Assessment of rAAV-Delivered Retinol Dehydrogenase 12 (RDH12) Activity.
Gene replacement therapy can be used for the treatment of hereditary retinopathies, such as retinol dehydrogenase 12 (RDH12)-associated Leber congenital amaurosis 13 (LCA13); however, the lack of animal models accurately mimicking the human disease phenotype requires the initial in vitro confirmation of therapy efficacy. Two synthetic serotypes (2.7m8 and PHP.S) of adeno-associated virus (AAV) were tested against the natural serotypes (5 and 9) with the aim of increasing the transduction efficiency and delivery of the green fluorescent protein (GFP) in HEK293 and ARPE-19 cells. The three most efficient serotypes were then used for the delivery of RDH12, followed by the assessment of its functional activity in the transduced cells. In the in vitro test system, a cassette encoding GFP and the wild-type (wt) RDH12 was delivered into ARPE-19 and HEK293 cells by rAAV 5, PHP.S, and 7m8 at 30K and 60K VG/cell. RDH12 mutants pThr155Ile (RDH12mut) and Met1* (RDH12sc) were used to mimic the RDH12-associated pathology. Transduction efficiency and protein expression were assessed by flow cytometry, fluorescence microscopy, and Western blotting. Percentages of AAV7m8-transduced GFP+ cells 1.5- and 6.4-times higher were observed as compared to AAV5 and AAV.PHP.S, respectively. 4-hydroxynonenal (4-HNE), more toxic to the cells with dysfunctional RDH12, was used on cells expressing the three RDH12wt versions. Following treatment with 100 μM 4-HNE, 2.6 (AAV5) and 8.8 (AAV7m8) times more cells co-expressing RDH12wt and GFP were alive as compared to the cells expressing only GFP. The number of live RDH12wt-expressing cells was also 32 and 9.6 times higher than that of RDH12sc-expressing cells and the negative control (NC), respectively. The developed approach enables the functional assessment of RDH12 replacement therapy only in rAAV-transduced cells and demonstrates that rAAV7m8 is the most efficient serotype for this purpose.
Biallelic germline variants in the hematologic malignancy predisposition gene DDX41 cause retinal dystrophy through dysregulation of retinal homeostasis.
Leber congenital amaurosis (LCA) and Early-onset severe retinal dystrophy (EOSRD) manifest within the first months and the first years of life, respectively. They are the leading cause of severe vision impairment in childhood. Using next generation sequencing, we identified eight families of patients with LCA/EOSRD carrying biallelic combination of six germline variants in DDX41 , encoding a DEAD-box ATPase RNA helicase involved in RNA splicing, innate immunity and hematopoiesis. In fibroblasts from a patient carrying the homozygous missense variant c.1187T>C (p. Ile396Thr) and in the retina of Ddx41 I396T/I396T mice, DDX41 protein expression was decreased. Electroretinogram recordings in these animals also revealed significant visual dysfunction since the first month of age, supporting a pathogenic role of DDX41 in retinal physiology. Immunohistochemical staining showed that the protein localized to nuclei in all major retinal cell types and to photoreceptor synapses, while biochemical assays showed that LCA/EOSRD variants disrupt DDX41 interactions with RNA through misfolding or the formation of non-productive aggregates, resulting in loss-of-function. Transcriptomic profiling of mutant mouse retinas revealed dysregulation of gene networks associated with Müller cells (MCs), glial cells essential for maintaining retinal structure, metabolic balance, and immune surveillance. The dysregulated pathways chiefly involved cell morphogenesis and junction formation, consistent with immunohistological analyses of widespread architectural disruption and nuclear disorganization, identifying MCs as a site of dysfunction. Together, these findings establish for the first time the involvement of DDX41 in LCA/EOSRD and provide new insights into the role of helicases in retinal homeostasis.
Combination gene therapy with AAV based RPE65 and survivin vectors sustains phenotypic rescue in neural retina of LCA2 mice.
Leber congenital amaurosis type 2 (LCA2) is an inherited retinal disorder, with severe vision impairment in children, progressing to complete blindness in the later stages of life. The current approved treatment involves Adeno-associated virus (AAV) vector serotype 2-based subretinal delivery of human RPE65 gene. However, long-term follow-up have reported gradual loss of phenotypic response. To overcome this, we have pursued strategies aimed at improving the transduction efficacy of the vector, optimizing the transgene for enhanced protein expression and co-delivering the therapeutic vector along with the anti-apoptotic factor, Survivin /baculoviral IAP repeat containing 5 (BIRC5) gene in the neural retina. We tested the efficacy of modified RPE65 transgene (Kozak/ codon optimized [CodOpt]) carried by an improved AAV2 vector (AAV2K665Q) against RPE65 wild type (WT) and observed that vector carrying CodOptRPE65 performed 1.8-fold better in vitro. Subsequently, the codon optimized RPE65 transgene containing vector was evaluated in a pre-clinical mouse model of LCA2 (rd12) with co-delivery of Survivin in an AAV5 vector. Animals were monitored for up to 6 months, and electroretinography revealed improved A- and B-wave response of 2.57- fold and 1.76-fold, respectively in combination treated eyes (CodOptRPE65 + Survivin) as compared to mock group. Co-delivery of CodOptRPE65 + Survivin did not significantly enhance retinal function by ERG when compared to AAV2K665Q-CMV-codon-optimized RPE65 alone. However, immunohistochemistry revealed that expression of apoptotic marker Bax is significantly reduced and anti-apoptotic marker Bcl2 significantly increased in animals receiving the combination therapy. A TUNEL assay further confirmed the decrease in apoptosis in the combination treatment group. These findings suggest that incorporating anti-apoptotic factors may strengthen the phenotypic rescue and control degeneration of the neural retina in LCA2 patients, offering a promising avenue for future clinical implementation.
Novel Genotype-Phenotype Correlations in CRB1-Retinopathies: Insights from Isoforms and Protein Domains Linked to Disease Severity.
This study evaluates genotype-phenotype correlations in CRB1-retinopathies using standardized phenotypic classification and comprehensive analysis of Crumbs homolog 1 (CRB1)-A and CRB1-B involvement alongside in silico protein modeling analysis. Retrospective multicenter cohort study. A total of 389 patients with biallelic disease-causing CRB1 variants from 50 international cohorts, including 73 patients from Moorfields Eye Hospital. Phenotypes were reclassified using standardized diagnostic criteria. Genotype-phenotype correlations were assessed based on CRB1 isoform involvement and protein domain localization of variants, supported by in silico structural modeling. Associations between CRB1 variant location, isoform involvement, and clinical phenotypes including Leber congenital amaurosis/early onset severe retinal dystrophy (LCA/EOSRD), retinitis pigmentosa (RP), cone-rod dystrophy, and macular dystrophy (MD). All patients had variants affecting CRB1-A, with none exclusively affecting CRB1-B. Mutations specific to CRB1-A, sparing CRB1-B were associated with MD. Mutations in exons 6, 7, and 9 were associated to LCA/EOSRD and RP phenotypes, whereas exon 2 variants were linked to MD. Genotype-phenotype correlations included c.1841G>T p.(Gly614Val) linked to LCA/EOSRD and variants exclusively involving exon 11 and 12. Similarly, the variants c.2506C>A p.(Pro836Thr) and c.498_506del p.(Ile167_Gly169del) were linked to MD. Crumbs homolog 1-A must be affected for disease manifestation, while sparing of CRB1-B leads to milder phenotypes. Novel genotype-phenotype correlations were found using standardized phenotypic classification. Understanding protein structure and isoform involvement is crucial for accurate diagnosis, prognosis, and the development of targeted therapies. The authors have no proprietary or commercial interest in any materials discussed in this article.
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American journal of ophthalmology case reportsConPath 2.0: an optimized consensus strategy for assessing the potential pathogenicity of hRPE65 missense variants.
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Molecular biology reports[Analysis of clinical manifestations and genetic variants among 11 Chinese pedigrees affected with Leber congenital amaurosis].
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical geneticsLeber Congenital Amaurosis.
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Advances in experimental medicine and biologyFrequency and Pattern of Gene Therapy Clinical Trials for Inherited Retinal Diseases.
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Pharmacological researchA Novel Variant in TUBB4B Causes Progressive Cone-Rod Dystrophy and Early Onset Sensorineural Hearing Loss.
Molecular genetics & genomic medicineNon-Viral Delivery Systems to Transport Nucleic Acids for Inherited Retinal Disorders.
Pharmaceuticals (Basel, Switzerland)Genotype-phenotype correlations for 17 Chinese families with inherited retinal dystrophies due to homozygous variants.
Scientific reportsA Korean Patient With Leber Congenital Amaurosis and a Homozygous RPE65 Variant Originating From a Paternal Uniparental Isodisomy.
Molecular genetics & genomic medicineInsights into the effects of subretinal voretigene neparvovec-rzyl in RPE65-associated Leber congenital amaurosis.
Canadian journal of ophthalmology. Journal canadien d'ophtalmologie"Blindness" is not a contraindication for voretigene neparvovec-rzyl treatment: a review of 9 cases.
Canadian journal of ophthalmology. Journal canadien d'ophtalmologieRabin8 phosphorylated by NDR2, the canine early retinal degeneration gene product, directs rhodopsin Golgi-to-cilia trafficking.
Journal of cell sciencePhenotypic and Genetic Heterogeneity of a Pakistani Cohort of 15 Consanguineous Families Segregating Variants in Leber Congenital Amaurosis-Associated Genes.
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Indian journal of ophthalmologyClinical Characterization, Natural History, and Detailed Phenotyping of NMNAT1-Associated Leber Congenital Amaurosis.
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Life (Basel, Switzerland)[Polymorphism and modern diagnostic approaches for Leber congenital amaurosis].
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Journal of medical geneticsRecombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review.
Molecular therapy : the journal of the American Society of Gene TherapyBystander base editing interferes with visual function restoration in Leber congenital amaurosis.
bioRxiv : the preprint server for biologyCas9-targeted-based long-read sequencing for genetic screening of RPE65 locus.
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Stem cell researchClinical, Genetic, and Histopathological Characteristics of CRX-associated Retinal Dystrophies.
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American journal of ophthalmologyWhole-Exome Sequencing in Turkish Patients with Inherited Retinal Dystrophies Reveals Novel Variants in Ten Genes.
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Communications biologyAblation of Fatty Acid Transport Protein-4 Enhances Cone Survival, M-cone Vision, and Synthesis of Cone-Tropic 9-cis-Retinal in rd12 Mouse Model of Leber Congenital Amaurosis.
The Journal of neuroscience : the official journal of the Society for NeuroscienceScreening for Autism Spectrum Disorder in Children and Adolescents With Leber's Congenital Amaurosis.
American journal of ophthalmologyClinical, Ophthalmic, and Genetic Characterization of RPGRIP1-Associated Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy.
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Scientific reportsClinical and genetic studies for a cohort of patients with Leber congenital amaurosis.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle OphthalmologieGeneration of two induced pluripotent stem cell lines (LVPEIi004-A and LVPEIi005-A) from probands with Leber Congenital Amaurosis 2 (LCA2) and harboring mutations in RPE65.
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BMC ophthalmologyQuantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3500 Inherited Retinal Disease Patients from the United Kingdom.
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Brain : a journal of neurologyAutosomal Recessive Rod-Cone Dystrophy with Mild Extra-Ocular Manifestations Due to a Splice-Affecting Variant in BBS9.
Current issues in molecular biologyDisease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases.
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Stem cell researchAutozygome-guided exome-first study in a consanguineous cohort with early-onset retinal disease uncovers an isolated RIMS2 phenotype and a retina-enriched RIMS2 isoform.
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Investigative ophthalmology & visual scienceExpanding the Genotype-Phenotype Correlations and Mutational Spectrum in Inherited Retinal Diseases: Novel and Recurrent Mutations.
CureusCharacteristics of Eyes With CRB1-Associated EOSRD/LCA: Age-Related Changes.
American journal of ophthalmologyEffective AAV-mediated gene replacement therapy in retinal organoids modeling AIPL1-associated LCA4.
Molecular therapy. Nucleic acidsCRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.
CellNormal vision and development in mice with low functional expression of Kir7.1 in heterozygosis for a blindness-producing mutation inactivating the channel.
American journal of physiology. Cell physiologyRPE65 mutations in Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitis pigmentosa from a tertiary eye care center in India.
Ophthalmic geneticsCould internal limiting membrane peeling before Voretigen neparvovec-ryzl subretinal injection prevent focal chorioretinal atrophy?
HeliyonThe Clinical Findings, Pathogenic Variants, and Gene Therapy Qualifications Found in a Leber Congenital Amaurosis Phenotypic Spectrum Patient Cohort.
International journal of molecular sciencesPhenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
Progress in retinal and eye researchUnlocking therapeutic potential: dual gene therapy for ameliorating the disease phenotypes in a mouse model of RPE65 Leber congenital amaurosis.
Frontiers in medicineRNA-Seq Analysis of Trans-Differentiated ARPE-19 Cells Transduced by AAV9-AIPL1 Vectors.
International journal of molecular sciencesUnique phenotypic-genotypic correlation in Saudi patients with ALMS1 mutations.
Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological SocietyFrequency and Pattern of Worldwide Ocular Gene Therapy Clinical Trials up to 2022.
BiomedicinesHIGH MYOPIA IS COMMON IN PATIENTS WITH X-LINKED RETINOPATHIES: Myopic Maculopathy Analysis.
Retina (Philadelphia, Pa.)Diagnostic Challenges in ABCA4-Associated Retinal Degeneration: One Gene, Many Phenotypes.
Diagnostics (Basel, Switzerland)Update on gene therapies in pediatric ophthalmology.
Archives de pediatrie : organe officiel de la Societe francaise de pediatriePatient stem cell-derived in vitro disease models for developing novel therapies of retinal ciliopathies.
Current topics in developmental biologyApplication of patient-derived induced pluripotent stem cells and organoids in inherited retinal diseases.
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Documenta ophthalmologica. Advances in ophthalmologyAn Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy.
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Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle OphthalmologieFoveal Hypoplasia in CRB1-Related Retinopathies.
International journal of molecular sciencesGene Therapy in Hereditary Retinal Dystrophies: The Usefulness of Diagnostic Tools in Candidate Patient Selections.
International journal of molecular sciencesThe Structural Abnormalities Are Deeply Involved in the Cause of RPGRIP1-Related Retinal Dystrophy in Japanese Patients.
International journal of molecular sciencesPNPLA6 disorders: what's in a name?
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Documenta ophthalmologica. Advances in ophthalmologyClinical and Genetic Characterization of RDH12-Retinal Dystrophy in a South American Cohort.
Ophthalmology. RetinaCell-based Therapies for Corneal and Retinal Disorders.
Stem cell reviews and reportsClassification and Growth Rate of Chorioretinal Atrophy after Voretigene Neparvovec-Rzyl for RPE65-Mediated Retinal Degeneration.
Ophthalmology. RetinaReduced ADP off-rate by the yeast CCT2 double mutation T394P/R510H which causes Leber congenital amaurosis in humans.
Communications biologyMetabolic changes and retinal remodeling in Heterozygous CRX mutant cats (CRXRDY/+).
Experimental eye research[Inherited retinal diseases in Germany-Challenges in health care supply structure and diagnostics].
Die OphthalmologieNovel Variant IMPDH1 c.134A>G, p.(Tyr45Cys): Phenotype-Genotype Correlation Revealed Likely Benign Clinical Significance.
International journal of molecular sciencesNonviral base editing of KCNJ13 mutation preserves vision in a model of inherited retinal channelopathy.
The Journal of clinical investigationDevelopment of a novel prediction model based on protein structure for identifying RPE65-associated inherited retinal disease (IRDs) of missense variants.
PeerJCRB1 is required for recycling by RAB11A+ vesicles in human retinal organoids.
Stem cell reportsA multidisciplinary approach to inherited retinal dystrophies from diagnosis to initial care: a narrative review with inputs from clinical practice.
Orphanet journal of rare diseasesBilateral exudative retinal detachments after subretinal gene therapy with voretigene neparvovec-rzyl for RPE65 Leber Congenital Amaurosis.
American journal of ophthalmology case reportsGene therapy for heart failure and cardiomyopathies.
Revista espanola de cardiologia (English ed.)Qualitative exploration of the visual function impairments and impacts on vision-dependent activities of daily living in Retinitis Pigmentosa and Leber Congenital Amaurosis: content validation of the ViSIO-PRO and ViSIO-ObsRO measures.
Journal of patient-reported outcomesComparison of Worldwide Disease Prevalence and Genetic Prevalence of Inherited Retinal Diseases and Variant Interpretation Considerations.
Cold Spring Harbor perspectives in medicineClinical, genetic, and structural characterization of a novel TUBB4B tubulinopathy.
Molecular genetics and metabolism reportsCurrent Advancements in Mouse Models of Retinal Disease.
Advances in experimental medicine and biologyGene Augmentation for Autosomal Dominant CRX-Associated Retinopathies.
Advances in experimental medicine and biologyAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
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Comunidades
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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.
- Establishment of an induced pluripotent stem cell line from a patient with Leber Congenital Amaurosis.
- Functional In Vitro Assessment of rAAV-Delivered Retinol Dehydrogenase 12 (RDH12) Activity.
- Biallelic germline variants in the hematologic malignancy predisposition gene DDX41 cause retinal dystrophy through dysregulation of retinal homeostasis.
- Combination gene therapy with AAV based RPE65 and survivin vectors sustains phenotypic rescue in neural retina of LCA2 mice.
- Novel Genotype-Phenotype Correlations in CRB1-Retinopathies: Insights from Isoforms and Protein Domains Linked to Disease Severity.
- Oxidative DNA damage drives apoptotic photoreceptor loss in NMNAT1-associated inherited retinal degeneration: a therapeutic opportunity.
- Isolated bull's eye maculopathy in two siblings with biallelic TULP1 variants.
- Novel compound heterozygous variants in NMNAT1 associated with leber congenital amaurosis: clinical and mutational profiles.
- Crop-OCT: a Fully Integrated Imageomics Pipeline to Identify Regional and Focal Retinopathy in Murine Models.
- Retinal gene therapies for inherited ocular diseases: Translational delivery strategies from bench to bedside.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:65(Orphanet)
- MONDO:0018998(MONDO)
- GARD:634(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Artigo Wikipedia(Wikipedia)
- Q1811132(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.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
