SLURP1 和 DSG1 中的新型无义变异导致巴基斯坦家族性掌跖角化病。
Novel nonsense variants in SLURP1 and DSG1 cause palmoplantar keratoderma in Pakistani families.
机构信息
Department of Biological Sciences, International Islamic University, H-10, Islamabad, 44000, Pakistan.
College of Medicine and Health, RILD Wellcome Wolfson Centre, University of Exeter, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW, UK.
出版信息
BMC Med Genet. 2019 Aug 23;20(1):145. doi: 10.1186/s12881-019-0872-1.
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.
背景
遗传性掌跖角化病（PPK）是一组具有临床和遗传异质性以及表型多样性的遗传性皮肤病，其特征为手掌和脚底过度角化。已有超过 20 个基因被报道与 PPK 相关，包括桥粒芯糖蛋白 1（DSG1），它是表皮黏附和分化的关键分子成分。黑棘皮病（MDM）是一种罕见的遗传性常染色体隐性遗传皮肤病，表现为移行性 PPK，与分泌型 LY6/PLAUR 结构域包含 1（SLURP1）基因突变有关。
方法
本研究描述了两个巴基斯坦家系共 12 名 PPK 患者的临床和遗传全外显子组测序（WES）和双脱氧测序研究。
结果
WES 鉴定出 SLURP1 中的一个新的纯合无义变异，以及 DSG1 中的一个新的杂合无义变异，可能是每个家系发病的原因。
结论
本研究扩展了 PPK 的分子基础知识，为来自巴基斯坦的 PPK 家系的临床管理提供了重要信息。
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