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is missing (Quiz).
Assuntos
Ceratodermia Palmar e Plantar/genética , Biópsia , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Humanos , Queratina-1/genética , Pessoa de Meia-Idade , MutaçãoRESUMO
BACKGROUND: Symmetrical acral keratoderma (SAK) is a rare skin disorder and its pathogenesis and inheritability are unknown. OBJECTIVES: To investigate the inheritance and pathogenesis of SAK. METHODS: Four SAK cases occurred in a four-generation Chinese family. Exome sequencing identified SNPs with potential SAK-related mutations, and a potentially responsible gene transcription factor 4 (TCF4) was identified. TCF4 was then sequenced in all 11 family members, and pedigree analysis was performed. Histopathology and immunohistochemistry evaluated TCF4 expression in skin lesions. The gene mutation was investigated in human keratinocytes for keratin-related protein expression. RESULTS: A novel heterozygous missense mutation, c.85C>A (p.Pro29Thr) was found in TCF4. The mutation showed autosomal dominant inheritance and perfectly cosegregated with the SAK phenotype in all family members. In skin lesions, TCF4 was present in the cytoplasm and membranes of the basal layer, the stratum spinosum and the stratum granulosum of the epidermis. The mutant TCF4 induced overexpression of differentiation markers including KRT1, KRT14, loricrin and involucrin. CONCLUSIONS: A SAK-related gene mutation in TCF4 may function through transcriptional regulation of keratin.
Assuntos
Povo Asiático/genética , Ceratodermia Palmar e Plantar/genética , Fator de Transcrição 4/genética , Proliferação de Células , Análise Mutacional de DNA , Epiderme/metabolismo , Exoma , Feminino , Heterozigoto , Humanos , Queratina-1/genética , Queratina-1/metabolismo , Queratina-14/genética , Queratina-14/metabolismo , Ceratodermia Palmar e Plantar/metabolismo , Ceratodermia Palmar e Plantar/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto , Linhagem , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Fator de Transcrição 4/metabolismoRESUMO
Background Acquired palmoplantar keratodermas (PPKs) pose diagnostic and therapeutic challenges due to their varied clinical presentations and overlapping features. This study aims to elucidate diagnostic criteria; assess correlations between clinical, dermoscopic, and histopathological features; and evaluate treatment outcomes for acquired PPKs, particularly palmoplantar psoriasis. Methods A prospective, cross-sectional study will be conducted at the Department of Dermatology, Venereology, and Leprosy, Acharya Vinoba Bhave Rural Hospital (AVBRH), Wardha, Maharashtra. Patients with acquired PPKs will undergo comprehensive clinical, dermoscopic, and histopathological evaluations. Treatment outcomes for palmoplantar psoriasis will be assessed following standard therapy. Statistical analysis will include descriptive statistics, diagnostic accuracy assessments, correlation analyses, and treatment outcome evaluations. Results The study is anticipated to establish reliable diagnostic criteria for acquired PPKs, identify correlations between features, and demonstrate the effectiveness of standard therapies for palmoplantar psoriasis. The findings are expected to inform evidence-based guidelines and protocols for diagnosing and managing acquired PPKs. Conclusion This study aims to advance the understanding and management of acquired PPKs by providing insights into diagnostic accuracy, correlations between features, and treatment outcomes. The study seeks to enhance patient care and outcomes for individuals affected by acquired PPKs by improving diagnostic precision and guiding therapeutic interventions.
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BACKGROUND: Skin lesions on the feet and foot deformities impair daily activities and decrease quality of life. Although substantial foot deformities occur in many genodermatoses, few reports have been published on this topic. Therefore, we performed a retrospective chart review to identify patients with genodermatoses and foot disorders. We included 16 patients, who were investigated clinically and with molecular biology. RESULTS: The following genodermatoses with foot deformities were detected: autosomal recessive congenital ichthyosis (ARCI, n = 7); palmoplantar keratodermas (PPKs, n = 6); ichthyosis follicularis, atrichia, and photophobia (IFAP, n = 1); ectrodactyly-ectodermal dysplasia-clefting (EEC, n = 1); and ichthyosis with confetti (IWC, n = 1). Foot problems not only varied in severity depending on the disease but also showed phenotypic heterogeneity among patients with the same condition. Foot deformities were most pronounced in patients with EEC (split foot) or IWC (contractures) and less severe in those with ARCI (clawed toes), IFAP (hollow feet), or PPK (no bone abnormalities in the feet). CONCLUSION: Because a range of distinct genodermatoses involve foot abnormalities, early rehabilitation and other corrective measures should be provided to patients with foot involvement to improve gait and prevent/delay irreversible complications.