RESUMO
Progressive symmetric erythrokeratodermia (PSEK) comprises a group of clinically and genetically heterogeneous diseases. Previous research have identified GJB3 and GJB4 as the leading genetic causes of this disorder. With the rapid development of genetics, GJA1, KDSR, KRT83 and TRPM4 have been identified as the new causative genes for PSEK, leading to a further understanding of its clinical features and genetic mechanisms. It's worth noting that Nagashima-type palmoplantar keratosis was often misdiagnosed as PSEK by our domestic dermatologists. Due to the identification of SERPINB7 as the causative gene of Nagashima-type palmoplantar keratosis recently, differentiation between the two disorders could be easily distinguished.
Assuntos
Eritroceratodermia Variável , Ceratodermia Palmar e Plantar , Eritroceratodermia Variável/diagnóstico , Eritroceratodermia Variável/genética , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/genéticaRESUMO
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Assuntos
Humanos , Feminino , Adolescente , Eritroceratodermia Variável/diagnóstico , Eritroceratodermia Variável/tratamento farmacológico , Mãos/patologia , Dermatoses do Pé/patologia , Imunoglobulina M/análiseAssuntos
Códon sem Sentido , Desmogleína 1/genética , Eritroceratodermia Variável/genética , Heterozigoto , Ceratodermia Palmar e Plantar/genética , Serpinas/genética , Adulto , Biópsia , Análise Mutacional de DNA , Eritroceratodermia Variável/diagnóstico , Predisposição Genética para Doença , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Masculino , Linhagem , Fenótipo , Pele/ultraestruturaAssuntos
Conexina 43/genética , Eritroceratodermia Variável/genética , Junções Comunicantes/metabolismo , Mutação de Sentido Incorreto , Pele/metabolismo , Criança , Conexina 43/química , Conexina 43/metabolismo , Análise Mutacional de DNA , Eritroceratodermia Variável/diagnóstico , Eritroceratodermia Variável/metabolismo , Feminino , Junções Comunicantes/patologia , Predisposição Genética para Doença , Humanos , Fenótipo , Conformação Proteica , Pele/patologia , Relação Estrutura-AtividadeAssuntos
Eritroceratodermia Variável/diagnóstico , Acitretina/uso terapêutico , Pré-Escolar , Fármacos Dermatológicos/uso terapêutico , Eritroceratodermia Variável/tratamento farmacológico , Eritroceratodermia Variável/genética , Eritroceratodermia Variável/patologia , Humanos , Masculino , Ureia/uso terapêuticoRESUMO
IMPORTANCE: The autosomal dominant spinocerebellar ataxias (SCAs) are a complex group of neurodegenerative disorders with significant genetic heterogeneity. Despite the identification of 20 SCA genes, the cause of the disorder in a significant proportion of families with SCA remains unexplained. In 1972, a French-Canadian family segregating a combination of SCA and erythrokeratodermia variabilis (EKV) in an autosomal dominant fashion was described. OBJECTIVE: To map and identify the causative gene in this large family with SCA and EKV using a combination of linkage analysis and whole-exome sequencing. DESIGN, SETTING, AND PARTICIPANTS: A total of 32 individuals from the family have undergone complete neurologic and dermatologic examinations. MAIN OUTCOMES AND MEASURES: Mutations in ELOVL4 have been reported in families with macular degeneration. Recently, homozygous mutations were found in patients with ichthyosis, spastic paraplegia, and severe neurodevelopmental defects. In the present study, we report on a heterozygote mutation in ELOVL4 in affected individuals from the family with SCA and EKV. The mutation segregates with a milder phenotype consisting of early-onset patches of erythema and hyperkeratosis, as well as SCA manifesting in the fourth or fifth decade of life. RESULTS: We describe the mapping and the identification of a c.504G>C transversion in ELOVL4 resulting in the p.L168F substitution. We also provide clinical characterization of the phenotypes in 19 mutation carriers. CONCLUSIONS AND RELEVANCE: We report, to our knowledge, the first mutation in ELOVL4 that is associated with SCA and EKV. This gene encodes a member of the elongase family, which is responsible for the elongation of very long-chain fatty acids (at least 26 carbons). These fatty acids participate in a wide variety of physiological functions, including skin barrier formation and peroxisome ß-oxidation. Overall, these results provide additional insight into the pathogenesis of these complex neurodegenerative disorders.
Assuntos
Eritroceratodermia Variável/genética , Proteínas do Olho/genética , Proteínas de Membrana/genética , Mutação de Sentido Incorreto/genética , Fenótipo , Ataxias Espinocerebelares/genética , Sequência de Aminoácidos , Estudos de Coortes , Eritroceratodermia Variável/diagnóstico , Eritroceratodermia Variável/etnologia , Feminino , Triagem de Portadores Genéticos , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Quebeque/etnologia , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/etnologiaRESUMO
BACKGROUND: Erythrokeratodermia variabilis (EKV) is a rare genodermatosis associated with keratinisation disorders. Mutations are found in genes encoding connexin 31 and 30.3 mapped to chromosome 1 p34-35. We report two cases of EKV, one of which presented dramatic improvement with oral retinoids. PATIENTS AND METHODS: A 15-month-old boy was referred to us with reddish-brown hyperkeratotic and well-demarcated plaques on the extremities, axillary space and face. The lesions started when he was 6months of age. Cutaneous histopathology showed acanthosis and papillomatosis associated with orthokeratotic hyperkeratosis. Anatomoclinical comparison confirmed the diagnosis of EKV. A second child aged 10years was referred to us with fixed, well-demarcated hyperkeratotic plaques associated with transient red patches. The lesions began when she was 1month old. Anatomoclinical comparison confirmed the diagnosis of EKV and the patient showed dramatic improvement after 2weeks on acitretin. DISCUSSION: EKV is characterized by the association of fixed well-demarcated plaques and transient erythematous patches. Although cutaneous histopathology is not specific, a typical physical examination and a compatible cutaneous histopathology can aid the diagnosis. Oral retinoids are often very rapidly effective.
