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. 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. 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. This study expands knowledge regarding the molecular basis of PPK, providing important information to aid clinical management in families with PPK from Pakistan.

中文翻译：

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SLURP1和DSG1中的新的无意义变异导致巴基斯坦家庭的掌足角化病

遗传性掌plant角化病（PPKs）是临床和遗传上异质的表型多样化的一组，以手掌和脚底过度角化为特征。据报道，有20多个基因与PPK相关，包括桥粒芯蛋白1（DSG1）是表皮粘附和分化的关键分子成分。Mal de Meleda（MDM）是一种罕见的遗传性常染色体隐性遗传性皮肤病，其特征是transgrediens PPK，与含1（SLURP1）基因的分泌LY6 / PLAUR域中的突变有关。这项研究描述了在巴基斯坦的两个家庭中的临床以及基因全基因组测序（WES）和双脱氧测序研究，共有12个人受到PPK的影响。WES在SLURP1中鉴定了一个新的纯合性无意义变体，DSG1中的一个新的杂合性废话变体，可能是每个家庭中这种情况的原因。这项研究扩展了有关PPK分子基础的知识，为帮助巴基斯坦PPK家族的临床管理提供了重要信息。