A survey on mutation spectrum in Iranian patients with limb-girdle muscular dystrophies

Limb-girdle muscular dystrophies (LGMD) designate diverse types of muscular dystrophies that predominantly affect proximal skeletal muscles. Although both autosomal recessive and dominant forms exist, the majority of cases are inherited in an autosomal recessive manner. Since the spectrum of genetic variants that cause this disorder is quite broad, next-generation sequencing techniques are the best diagnostic tools for LGMD. In this study, we provide an overview of mutation spectrum of LGMD-related genes in the Iranian patients using whole exome sequencing. Notably, CAPN3 and LAMA2 genes were the genes encompassing the highest frequencies of pathogenic or likely pathogenic variants in this cohort. Pathogenic and likely pathogenic variants were identified in CAPN3 gene in total of 10 cases out of 48 cases tested (20%). In addition, different variants in each of POMGNT1 and TTN genes were detected in five and four patients, respectively. Three patients had DYSF variants (6%). While the inheritance of the majority of cases was supposed to be in an autosomal recessive manner, in three cases, the disease inheritance was best explained by the dominant type (c.947 C > T variant in the DNAJB6, c.746G > A variant in the LMNA, and c.1417G > A variant in the TNPO3). The current study broadens the spectrum of LGMD-related mutations among Iranian patients and facilitates genetic counseling in the affected families.