A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa

作     者：Sattar, Saira Bharadwaj, Thashi Kalsoom, Umm-e- Acharya, Anushree Khan, Saadullah Leal, Suzanne M. Schrauwen, Isabelle 

作者机构：Hazara Univ Dept Biochem Mansehra Kpk Pakistan Columbia Univ Ctr Stat Genet Gertrude H Sergievsky Ctr Dept NeurolMed Ctr New York NY 10032 USA Kohat Univ Sci & Technol Dept Biotechnol & Genet Engn Kohat Pakistan Columbia Univ Taub Inst Med Ctr New York NY USA Univ Arizona Coll Med Dept Translat Neurosci 475 N 5th St Phoenix AZ 85004 USA 

出 版 物：《BMC MEDICAL GENOMICS》 (BMC Med. Genomics)

年 卷 期：2025年第18卷第1期

页      面：1-7页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：Higher Education Commission, Pakistan Higher Education Commission (international research support initiative program) in Pakistan 

摘      要：Dystrophic epidermolysis bullosa is a rare subtype of inherited epidermolysis bullosa, caused by variants in the collagen type VII alpha 1 chain (COL7A1) gene (MIM120120). Both autosomal dominant and recessive inheritance has been reported with variable phenotype. We investigated a Pakistani family with dystrophic epidermolysis bullosa via exome sequencing and identified a pathogenic nonsense variant in COL7A1 NM_000094 c.1573 C T:p.(Arg525*). The inheritance pattern observed was consistent with a semi-dominant model, where heterozygous parents exhibited a mild phenotype, and homozygous children were more severely affected. For dystrophic epidermolysis bullosa, loss-of-function variants are typically associated with the autosomal recessive form, while missense variants are linked to the autosomal dominant form. A review of the literature suggests a semi-dominance pattern for some missense variants, particularly glycine substitutions, but this concept had not been formally recognized. This study highlights the importance of considering semi-dominant inheritance models for dystrophic epidermolysis bullosa and other Mendelian diseases with an autosomal recessive mode of inheritance, as it can significantly impact diagnosis and genetic counseling.