A Queratose tipo Nagashima é um problema de pele que causa um espessamento nas palmas das mãos e solas dos pés. Esse espessamento pode se estender um pouco para outras áreas (é "transgressiva"), mas não piora com o tempo (não é "progressiva"). Ela se parece com uma forma mais leve do Mal de Meleda.
Introdução
O que você precisa saber de cara
A Queratose tipo Nagashima é um problema de pele que causa um espessamento nas palmas das mãos e solas dos pés. Esse espessamento pode se estender um pouco para outras áreas (é "transgressiva"), mas não piora com o tempo (não é "progressiva"). Ela se parece com uma forma mais leve do Mal de Meleda.
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Entender a doença
Do básico ao detalhe, leia no seu ritmo
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Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 14 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
1 gene identificado com associação a esta condição. Padrão de herança: Autosomal recessive.
Might function as an inhibitor of Lys-specific proteases. Might influence the maturation of megakaryocytes via its action as a serpin
Cytoplasm
Keratoderma, palmoplantar, Nagashima type
An autosomal recessive, non-syndromic, diffuse palmoplantar keratosis characterized by well-demarcated diffuse erythematous hyperkeratosis expanding onto the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis is mild and non-progressive.
Variantes genéticas (ClinVar)
106 variantes patogênicas registradas no ClinVar.
Classificação de variantes (ClinVar)
Distribuição de 8 variantes classificadas pelo ClinVar.
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 — Queratodermia palmoplantar, tipo Nagashima
Selecione um estado ou use sua localização para ver resultados.
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Functional Characterization of a Novel In-Frame Indel and a Founder Variant in SERPINB7 Associated With Palmoplantar Keratoderma.
Nagashima-type palmoplantar keratoderma (NPPK) is a hereditary non-epidermolytic keratoderma predominantly reported in East Asian populations. It is mainly caused by biallelic loss-of-function variants in SERPINB7, but the functional impact of certain variants remains unclear. In this study, we performed Sanger sequencing on three unrelated Chinese patients with clinically diagnosed NPPK and identified biallelic pathogenic SERPINB7 variants in all cases. Among these, a novel in-frame indel variant (c.806_814delinsT, p.Ser269_Glu273delinsLeu) and three known founder variants (c.796C>T, c.522dupT, and c.455G>T) were detected. Transcript analysis revealed that the c.455G>T variant, despite being located at the exon-intron 6 junction, functions as a missense variant (p.Gly152Val) without affecting mRNA splicing. Functional studies, including protein structural modeling and legumain protease activity assays, revealed that both variants impaired the inhibitory function of SERPINB7, leading to increased legumain activity. These findings expand the mutational spectrum of SERPINB7 and provide new insights into the pathogenicity of the c.806_814delinsT and c.455G>T variants in the Chinese population.
A deep intronic founder variant in the SERPINB7 gene causing aberrant splicing is a potential therapeutic target for Nagashima-type palmoplantar keratoderma.
Nagashima-type palmoplantar keratoderma (NPPK), caused by biallelic SERPINB7 loss-of-function variants, lacks effective treatments. Intriguingly, monoallelic exonic variants are observed in some patients with NPPK, suggesting additional genetic variants. To characterize a deep intronic SERPINB7 variant's pathogenicity, elucidate its splicing dysregulation, and evaluate antisense oligonucleotide (ASO) therapy. A customized next-generation sequencing panel was applied to six Chinese NPPK patients. Pathological changes were analyzed by H&E staining and immunofluorescence. RNA extracted from palmar skin was assessed for splicing alterations. Plasmids were generated to evaluate the expression and function of mutant SERPINB7 protein. Haplotype analysis was conducted to confirm the founder effect. RNA pull-down assays and mass spectrometry were used to identify the key splicing factor. Minigene constructs were developed to characterize the splicing process in vitro. Finally, an ASO was designed to target this variant. A deep intronic SERPINB7 variant was identified in six NPPK patients, leading to pseudo-exon inclusion and the production of a truncated, dysfunctional SERPINB7 protein. Haplotype analysis confirmed it as a Chinese founder variant. RNA pull-down assays revealed excessive SRSF9 binding to the abnormal transcript. In vitro, the ASO successfully corrected the aberrant splicing. This study established the pathogenicity of a deep intronic founder variant in SERPINB7 driving NPPK via SRSF9-mediated splicing dysregulation, demonstrating ASO therapeutic potential. Findings provide mechanistic insights and a targeted approach for precision therapy development for NPPK.
SERPINA12 variants harboured in Nagashima-type palmoplantar keratoderma: Potential inflammatory characteristics.
Microbial dysbiosis and foot odor in Nagashima-type palmoplantar keratosis: Improvement with topical benzoyl peroxide.
Nagashima-type palmoplantar keratosis (also referred to as SERPINB7-related palmoplantar epidermal differentiation disorder) is the most common form of palmoplantar keratoderma in East Asia. It is characterized by erythematous hyperkeratosis, palmoplantar hyperhidrosis, and a distinctive foot odor that significantly impairs QOL. In this study, we aimed to clarify the etiology of this odor by investigating the plantar microbiome and evaluating the therapeutic effects of topical benzoyl peroxide. Compared with healthy controls, individuals with Nagashima-type palmoplantar keratosis exhibited significantly higher objective odor scores; increased bacterial load, especially in the intertoe area; and reduced microbial diversity. Corynebacterium and Staphylococcus were the predominant dysbiotic flora species. The topical application of benzoyl peroxide significantly reduced foot odor and bacterial load; increased microbial diversity; and selectively decreased Corynebacterium abundance, particularly that of C tuberculostearicum. These changes correlate with the species-specific susceptibility of skin-resident bacteria to benzoyl peroxide. Our findings suggest that microbial dysbiosis, especially the overgrowth of Corynebacterium species, is central to the pathogenesis of foot odor in Nagashima-type palmoplantar keratosis. Topical benzoyl peroxide is a promising therapeutic intervention for mitigating dysbiosis and its associated foot odor. This study highlights the potential of microbiome-targeted therapies for symptom relief in inherited skin disorders such as Nagashima-type palmoplantar keratosis.
Dupilumab treatment for Chinese Nagashima-type palmoplantar keratoderma associated with atopic dermatitis: a case report.
Patients with Nagashima-type palmoplantar keratoderma (NPPK) experience progressive, painful hyperkeratosis and fissuring of palms and soles that limits daily activities Due to the incomplete understanding of its pathogenesis, there are currently no effective treatments for NPPK. We report a 26-year-old woman with lifelong, worsening palmoplantar keratoderma, nail dystrophy, and concomitant atopic dermatitis refractory to topical treatments. Next-generation sequencing revealed compound heterozygous mutations in SERPINB7 (c.796C>T, p.Arg266Ter) and filaggrin (FLG, c.3321delA, p.Gly1109GlufsTer13), while her asymptomatic parents and brother carried only single heterozygous variants, underscoring the digenic pathogenesis in our patient. After 42 weeks of dupilumab treatment, palmoplantar keratosis and nail changes had almost completely resolved, and the eruption resembled mild chronic eczema. Dupilumab therefore appears to be a safe and effective option for digenic NPPK complicated by atopic dermatitis and warrants further investigation in larger cohorts.
Publicações recentes
The Contribution of Native Protein Complexes to Targeted Protein Degradation.
Keratin 16 inhibits type I interferon responses in differentiating keratinocytes of stressed and diseased skin.
Genetic palmoplantar keratoderma associated with SERPINA12 mutations.
Imaging Naxos Disease and Related Cardiocutaneous Syndromes: The NAXCARE Multimodality Approach.
"Starry Night Sign" in Pediatric Punctate Palmoplantar Keratoderma.
📚 EuropePMCmostrando 57
Functional Characterization of a Novel In-Frame Indel and a Founder Variant in SERPINB7 Associated With Palmoplantar Keratoderma.
The Journal of dermatologyMicrobial dysbiosis and foot odor in Nagashima-type palmoplantar keratosis: Improvement with topical benzoyl peroxide.
The Journal of investigative dermatologyDupilumab treatment for Chinese Nagashima-type palmoplantar keratoderma associated with atopic dermatitis: a case report.
Frontiers in immunologyA deep intronic founder variant in the SERPINB7 gene causing aberrant splicing is a potential therapeutic target for Nagashima-type palmoplantar keratoderma.
Journal of dermatological scienceSERPINA12 variants harboured in Nagashima-type palmoplantar keratoderma: Potential inflammatory characteristics.
Journal of dermatological scienceDigenic Biallelic Variants in SERPINB7 and SERPINA12 in a Patient With a Severe Phenotype of Nagashima-Type Palmoplantar Keratosis.
The Journal of dermatologyEstimating the proportions of allele frequencies for SERPINA12 pathogenic variants in Japanese patients with Nagashima-type palmoplantar keratosis/keratoderma.
The British journal of dermatologyHeterozygous Pathogenic Variants in SERPINB7 Potentially Associated With Concomitant Moyamoya Angiopathy and Nagashima-Type Palmoplantar Keratoderma.
American journal of medical genetics. Part AHistory and prospects of Nagashima-type palmoplantar keratosis, the most common palmoplantar keratoderma in east Asian populations.
The Journal of dermatologyPhenotypic and genotypic analysis of SERPINA12-related autosomal recessive palmoplantar keratoderma in southwestern China.
The Journal of dermatologyNagashima-type palmoplantar keratoderma.
Indian journal of dermatology, venereology and leprologyCoincidence of acral peeling skin syndrome and Nagashima-type palmoplantar keratosis in a Japanese pedigree with acral skin peeling.
The Journal of dermatologySERPINB7 Deficiency Increases Legumain Activity and Impairs the Epidermal Barrier in Nagashima-Type Palmoplantar Keratoderma.
The Journal of investigative dermatologyGenetic analysis of seven patients with inherited ichthyosis and Nagashima‑type palmoplantar keratoderma.
Molecular medicine reportsNagashima-type palmoplantar keratosis associated with Tc17 cells in a patient with rheumatoid arthritis.
European journal of dermatology : EJDPotential digenic inheritance of SERPINB7 and SERPINA12 variants in Chinese patients with Nagashima-type palmoplantar keratosis.
The British journal of dermatologySpontaneous clinical remission of Nagashima-type palmoplantar keratoderma in a patient of Korean descent with a heterozygous SERPINB7 mutation.
Pediatric dermatologyA novel SERPINA12 variant and first European patients with diffuse palmoplantar keratoderma.
Journal of the European Academy of Dermatology and Venereology : JEADVSERPINB7 mutation causes Nagashima-type palmoplantar keratosis and its spatiotemporal expression in zebrafish.
Experimental dermatologyNagashima-type palmoplantar keratoderma: Case series and two novel variants.
Pediatric dermatologyInvestigation of Nagashima-type palmoplantar keratoderma in China: A cross-sectional study of 234 patients.
The Journal of dermatologyThree new founder mutations in Chinese patients with Nagashima-type palmoplantar keratoderma.
The British journal of dermatologyImprovement of redness and hyperkeratosis in a case of Nagashima-type palmoplantar keratosis during Tofacitinib treatment for ulcerative colitis.
Journal of the European Academy of Dermatology and Venereology : JEADVTwo novel mutations of SERPINB7 in eight cases of Nagashima-type palmoplantar keratosis in the Chinese population.
The Journal of dermatologyIdentification of a Rare Case With Nagashima-Type Palmoplantar Keratoderma and 18q Deletion Syndrome via Exome Sequencing and Low-Coverage Whole-Genome Sequencing.
Frontiers in geneticsAcral peeling in Nagashima type palmo-plantar keratosis patients reveals the role of serine protease inhibitor B 7 in keratinocyte adhesion.
Experimental dermatologyUpdated allele frequencies of SERPINB7 founder mutations in Asian patients with Nagashima-type palmoplantar keratosis/keratoderma.
Journal of dermatological science[Diagnosis and progress in the progressive symmetric erythrokeratodermia].
Zhonghua yi xue za zhiNagashima-Type Palmoplantar Keratosis: Clinical Characteristics, Genetic Characterization, and Clinical Management.
BioMed research internationalEffect of Gentamicin Ointment in Patients with Nagashima-type Palmoplantar Keratosis: A Double-blind Vehicle-controlled Study.
Acta dermato-venereologicaNagashima-Type Palmoplantar Keratosis with Compound Heterozygous Mutations in SERPINB7.
Case reports in dermatologyNagashima-type palmoplantar keratosis caused by biallelic maternal mutation of SERPINB7 with segmental uniparental disomy of chromosome 18q.
The Journal of dermatologySERPINB7 novel mutation in Chinese patients with Nagashima-type palmoplantar keratosis and cases associated with atopic dermatitis.
International journal of dermatologyNagashima-type palmoplantar keratosis in Finland caused by a SERPINB7 founder mutation.
Journal of the American Academy of DermatologyA Case of Malignant Melanoma Arising in Nagashima-type Palmoplantar Keratosis.
Acta dermato-venereologica[Nagashima-type palmoplantar keratoderma: A little-known palmoplantar keratoderma in Europe].
Annales de dermatologie et de venereologieSymmetrical acral keratoderma revisited: proposal for a new term, 'pigmented carpotarsal hyperkeratosis'.
Journal of the European Academy of Dermatology and Venereology : JEADVNagashima-type palmoplantar keratoderma and malignant melanoma in Japanese patients.
The British journal of dermatologyCoexistence of X-linked ichthyosis and Nagashima-type palmoplantar keratosis: A case report.
The Journal of dermatologyA follow-up report of acral melanoma in a patient with Nagashima-type palmoplantar keratosis: validation of SERPINB7 mutation and local recurrence.
European journal of dermatology : EJDA novel frameshift SERPINB7 mutation in a Chinese case with Nagashima-type palmoplantar keratosis: case report and review of the literature.
Clinical and experimental dermatologyTopical Gentamicin for the Treatment of Genetic Skin Diseases.
The Journal of investigative dermatologyThree cases of Nagashima-type palmoplantar keratosis associated with atopic dermatitis: A diagnostic pitfall.
The Journal of dermatologyGentamicin-Induced Readthrough and Nonsense-Mediated mRNA Decay of SERPINB7 Nonsense Mutant Transcripts.
The Journal of investigative dermatologyNovel nonsense mutation in SERPINB7 and the treatment of foot odor in a patient with Nagashima-type palmoplantar keratosis.
The Journal of dermatologyNagashima-type palmoplantar keratosis with melanoma: absence of epidermal Langerhans cells in hyperkeratotic skin.
European journal of dermatology : EJDMultiple Primary Acral Lentiginous Melanoma on the Feet Developing in Lesions of Nagashima-type Palmoplantar Keratoderma.
Acta dermato-venereologicaDetection of SERPINB7 mutation can distinguish Nagashima-type palmoplantar keratoderma from other keratodermas with palmoplantar lesions.
Clinical and experimental dermatologyNagashima-type palmoplantar keratosis in a Chinese Han population.
Molecular medicine reportsA sporadic case of Nagashima-type palmoplantar keratosis caused by gene mutation in SERPINB7.
Clinical and experimental dermatologyNovel frame-shift mutation in SERPINB7 in a Japanese patient with Nagashima-type palmoplantar keratosis.
The Journal of dermatologyIdentification of SERPINB7 mutations in Korean patients with Nagashima-type palmoplantar keratosis.
The Journal of dermatologyProgressive Nagashima-type palmoplantar keratosis in a Chinese patient with recurrent c.796C>T mutation in SERPINB7.
Indian journal of dermatology, venereology and leprologyExtensive Erythema and Hyperkeratosis on the Extremities and Lumbar Area as an Unusual Mani-festation of Nagashima-type Palmoplantar Keratosis.
Acta dermato-venereologicaIdentification and Characterization of a Recessive Missense Mutation p.P277L in SERPINB7 in Nagashima-Type Palmoplantar Keratosis.
The Journal of investigative dermatologyIdentification of previously unknown SERPINB7 splice variants in patients with Nagashima-type palmoplantar keratosis reveals the importance of the CD-loop of SERPINB7.
The British journal of dermatologyNagashima-type palmoplantar keratosis caused by compound heterozygous mutations in SERPINB7.
European journal of dermatology : EJDAssociações
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.
- Functional Characterization of a Novel In-Frame Indel and a Founder Variant in SERPINB7 Associated With Palmoplantar Keratoderma.
- A deep intronic founder variant in the SERPINB7 gene causing aberrant splicing is a potential therapeutic target for Nagashima-type palmoplantar keratoderma.
- SERPINA12 variants harboured in Nagashima-type palmoplantar keratoderma: Potential inflammatory characteristics.
- Microbial dysbiosis and foot odor in Nagashima-type palmoplantar keratosis: Improvement with topical benzoyl peroxide.
- Dupilumab treatment for Chinese Nagashima-type palmoplantar keratoderma associated with atopic dermatitis: a case report.
- The Contribution of Native Protein Complexes to Targeted Protein Degradation.
- Keratin 16 inhibits type I interferon responses in differentiating keratinocytes of stressed and diseased skin.
- Genetic palmoplantar keratoderma associated with SERPINA12 mutations.
- Imaging Naxos Disease and Related Cardiocutaneous Syndromes: The NAXCARE Multimodality Approach.
- "Starry Night Sign" in Pediatric Punctate Palmoplantar Keratoderma.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:140966(Orphanet)
- OMIM OMIM:615598(OMIM)
- MONDO:0014272(MONDO)
- GARD:16967(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q55784760(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