Homozygous missense variant in POPDC3 causes recessive limb‐girdle muscular dystrophy type 26. (7th February 2022)

• Record Type: Journal Article
• Authors: Ullah, Anwar; Lin, Zhaohan; Younus, Muhammad; Shafiq, Sarfraz; Khan, Shazia; Rasheed, Memoona; Mahmood, Arif; Alqosaibi, Amany I.; Alshehri, Mohammed Ali; Khan, Amjad; Umair, Muhammad
• Is Part Of: Journal of gene medicine. Volume 24:Number 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-07
• Subjects: bi‐allelic -- LGMD -- limb‐girdle muscular dystrophies -- missense variant -- POPDC3 -- whole‐exome sequencing; Genetic transformation -- Periodicals; Gene Transfer -- Periodicals; Gene Therapy -- Periodicals; 616.042
• DOI: 10.1002/jgm.3412
• Languages: English
• ISSNs: 1099-498X

Abstract

Abstract: Background: Limb‐girdle muscular dystrophy (LGMD) comprises a heterogeneous group of diseases, affecting different muscles, predominantly skeletal muscles and cardiac muscles of the body. LGMD is classified into two main subtypes A and B, which are further subclassified into eight dominant and thirty recessive subtypes. Three genes, namely POPDC1, POPDC2 and POPDC3, encode popeye domain‐containing protein (POPDC), and the variants of POPDC1 and POPDC3 genes have been associated with LGMD. Methods: In the present study, we performed whole‐exome sequencing (WES) analysis on a single‐family to investigate the hallmark features of LGMD. The results of WES were further confirmed by Sanger sequencing and 3D protein modeling was also conducted. Results: WES data analysis and Sanger sequencing revealed a homozygous missense variant (c.460A>G; p.Lys154Glu) at a highly conserved amino acid position in the POPDC3. Mutations in the POPDC3 gene have been previously associated with recessive limb‐girdle muscular dystrophy type 26. 3D protein modeling further suggested that the identified variant might affect the POPDC3 structure and proper function. Conclusions: The present study confirms the role of POPDC3 in LGMD, and will facilitate genetic counseling of the family to mitigate the risks of the carrier or affects on future pregnancies. Abstract : A single‐family having hallmark features of LGMD was evaluated using whole exome sequencing and Sanger sequencing. A novel homozygous missense variant (c.460A>G; p.Lys154Glu) was identified that was conserved across different species. 3D protein modeling suggested that the variant might affect POPDC3 structure and function.