A Novel Homozygous Nonsense Mutation p.Cys366* in the WNT10B Gene Underlying Split-Hand/Split Foot Malformation in a Consanguineous Pakistani Family.

WNT10B 基因中一种新的纯合子无义突变 p. Cys366 * 是巴基斯坦近亲家庭中分裂手 / 分裂脚畸形的基础。

• 影响指数: 3.569
• 发表时间: 2019
• 来源期刊: Front Pediatr
• DOI: 10.3389/fped.2019.00526
• PMID: 31998667
• 文章类型: Case Reports
• 中科院分区: Q3
• 方向: 医学
• 作者列表: Khan A,Wang R,Han S,Umair M,Alshabeeb MA,Ansar M,Ahmad W,Alaamery M,Zhang X

关键词: Pakistani family; SHFM; autosomal recessive mode; gene variant; non-sense mutation

Abstract

Split hand/split foot malformation (SHFM) or ectrodactyly is characterized by a deep median cleft of the hand or foot, hypoplasia or aplasia of the metacarpals, metatarsals, and phalanges. It is a clinically and genetically heterogeneous group of limb malformations. This study aimed to identify the pathogenic variant in a consanguineous Pakistani family with autosomal recessive SHFM. Peripheral blood samples were obtained, DNA was extracted, WNT10B coding and noncoding regions were PCR amplified and Sanger sequencing was performed using workflow suggested by Thermo Fisher Scientific. A novel homozygous nonsense variant (c.1098C>A; p.Cys366*) was identified in the WNT10B gene in the index patients, which probably explains SHFM type 6 in this family in comparison with similar data from the literature.

摘要

裂手/裂脚畸形（SHFM）或外翻畸形的特征是手或脚的深正中裂，掌骨发育不全或发育不全，meta骨，和指骨。它是一组临床和遗传异质性的肢体畸形。这项研究旨在鉴定具有常染色体隐性遗传SHFM的近亲巴基斯坦家庭中的致病变异。获得外周血样本，提取DNA,PCR扩增WNT10B编码区和非编码区,并使用ThermoFisherScientific建议的工作流程进行Sanger测序。在索引患者的WNT10B基因中鉴定出一种新的纯合无义变体（c.1098C>A;p.Cys366*），与文献中的类似数据相比，这可能解释了该家族中的SHFM类型6。