A Spectrum of Pathogenic Variants in the LAMA2 Gene in the Russian Federation

LAMA2-associated muscular dystrophy is a rare genetic disorder caused by pathogenic or likely pathogenic variants in the LAMA2 gene. The aim of this study is to characterize the spectrum of pathogenic/likely pathogenic variants in the LAMA2 gene among Russian patients, identify frequent pathogenic variants specific to this population, and estimate the prevalence of this disorder in Russia. Data were collected and analyzed from patients with confirmed diagnoses of LAMA2-associated muscular dystrophy using various molecular genetic methods in research centers from 2008 to 2024. Data were obtained from 90 unrelated patients with LAMA2-associated muscular dystrophy, out of which 83 presented with the more severe form, MDC1A1, while seven had milder form of LAMA2-associated muscular dystrophy. The most common pathogenic variants identified were nonsense mutations (40% of cases), followed by frameshift variants (29.3%), splicing variants (21.4%), gross deletions (5.3%), and missense variants (4%). It is worth noting that missense variants were found exclusively in patients with the milder form of LAMA2-associated muscular dystrophy. The most prevalent identified pathogenic variant was c.7536del (15%), characteristic of Slavic populations with an established founder effect. Additionally, a common pathogenic variant, c.8245-2A>G, was found predominantly in Kazan Tatars. The estimated prevalence of LAMA2-associated muscular dystrophy in Russia is approximately 1 in 117,700.