Novel nonsense variants in SLURP1 and DSG1 cause palmoplantar keratoderma in Pakistani families

BMC Medical Genetics

Claire Prince¹  James Fasham¹  Gaurav V. Harlalka¹  Emma L. Baple¹  Chloe Payne¹  Andrew H. Crosby¹  Wasim Ahmad²  Asma Gul³  Abida Akbar³ 

[1] College of Medicine and Health, RILD Wellcome Wolfson Centre, University of Exeter, Royal Devon & Exeter NHS Foundation Trust;Department of Biochemistry, Faculty of Biological Sciences, Quaid-e-Azam University (QAU);Department of Biological Sciences, International Islamic University;

关键词: Mal de Meleda;    Palmoplantar keratoderma;    SLURP1;    DSG1;    Mutation;    Variant;   

DOI  :  10.1186/s12881-019-0872-1

来源: DOAJ

【 摘 要 】

Abstract Background Inherited palmoplantar keratodermas (PPKs) are clinically and genetically heterogeneous and phenotypically diverse group of genodermatoses characterized by hyperkeratosis of the palms and soles. More than 20 genes have been reported to be associated with PPKs including desmoglein 1 (DSG1) a key molecular component for epidermal adhesion and differentiation. Mal de Meleda (MDM) is a rare inherited autosomal recessive genodermatosis characterized by transgrediens PPK, associated with mutations in the secreted LY6/PLAUR domain containing 1 (SLURP1) gene. Methods This study describes clinical as well as genetic whole exome sequencing (WES) and di-deoxy sequencing investigations in two Pakistani families with a total of 12 individuals affected by PPK. Results WES identified a novel homozygous nonsense variant in SLURP1, and a novel heterozygous nonsense variant in DSG1, as likely causes of the conditions in each family. Conclusions This study expands knowledge regarding the molecular basis of PPK, providing important information to aid clinical management in families with PPK from Pakistan.

【 授权许可】

Unknown