Ayub Muhammad, Xiong Xing, Anwer Saima, Altmüller Janine, Naeem Muhammad, Hassan Noor, Khan Kafaitullah, Motameny Susanne, Khaliq Samira, Rehman Fazal Ur, Uddin Syed Ashraf, Wali Abdul, Betz Regina, Basit Sulman
Institute of Biochemistry, University of Balochistan, Quetta, Pakistan.
Institute of Human Genetics, Medical Faculty & University Hospital Bonn, University of Bonn, Bonn, Germany.
J Med Life. 2024 Sep;17(9):892-896. doi: 10.25122/jml-2024-0090.
Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of an inherited skin disorder. RDEB segregates both in an autosomal dominant as well as in an autosomal recessive pattern. It has been shown that both forms of dystrophic epidermolysis bullosa (DEB) are caused by mutations in the gene. In this study, we investigated a consanguineous four-generation family with two individuals displaying the RDEB phenotype. Both patients showed multiple skin erosions, atrophic scares, crusted scaling, and pseudosyndactyly. Whole exome sequencing (WES) was performed to identify the underlying genetic defect, revealing a homozygous nonsense mutation, c.409C>T (p.Arg137*) in in both patients. This variant was validated through Sanger sequencing and confirmed to segregate within the family. This report describes a recurrent nonsense mutation in that leads to a severe form of autosomal recessive dystrophic epidermolysis bullosa. Moreover, this study demonstrates that whole exome sequencing analysis is imperative in resolving clinically and genetically heterogeneous diseases like RDEB. Furthermore, this study expands the mutation spectrum of the gene in distinct populations.
常染色体隐性营养不良性大疱性表皮松解症（RDEB）是一种严重的遗传性皮肤病。RDEB以常染色体显性和常染色体隐性模式遗传。研究表明，两种形式的营养不良性大疱性表皮松解症（DEB）均由该基因的突变引起。在本研究中，我们调查了一个近亲四代家庭，其中两名个体表现出RDEB表型。两名患者均出现多处皮肤糜烂、萎缩性瘢痕、结痂鳞屑和并指畸形。进行全外显子组测序（WES）以确定潜在的基因缺陷，结果显示两名患者的该基因均存在纯合无义突变c.409C>T（p.Arg137*）。通过桑格测序验证了该变异，并证实其在家族中分离。本报告描述了该基因中导致严重常染色体隐性营养不良性大疱性表皮松解症的复发性无义突变。此外，本研究表明全外显子组测序分析对于解决像RDEB这样临床和遗传异质性疾病至关重要。此外，本研究扩展了该基因在不同人群中的突变谱。
