This systematic review identified a broad spectrum of pathogenic DYSF gene variants distributed across Arab populations from eight countries, with multiple recurrent and novel mutations associated with LGMDR2 and related myopathies.
Systematic Review
This systematic review maps the mutational spectrum of the DYSF gene in Arab populations, identifying 48 unique variants to facilitate diagnosis and inform public health strategies for dysferlinopathies.
Dysferlinopathies are a subset of autosomal recessive muscular dystrophies resulting from pathogenic variants in the dysferlin (DYSF) gene. The prevalence of dysferlinopathies remains inadequately defined. This review aims to elucidate the mutational spectrum of DYSF in Arab populations. A systematic search was conducted in PubMed, ScienceDirect, Scopus, and Web of Science up to September 15, 2025. We identified 48 unique DYSF variants documented in the literature across eight Arab countries, resulting in 49 country-entries due to one variant being reported in two countries. The distribution of reported variants was as follows: Saudi Arabia 32.7% (16/49), Algeria 20.4% (10/49), Egypt 20.4% (10/49), Tunisia 10.2% (5/49), Morocco 6.1% (3/49), Libya 4.1% (2/49), Lebanon 4.1% (2/49), and Oman 2.0% (1/49). Clinical presentations were categorized based on phenotype assignments across variants, totaling 52 assignments as some variants were associated with multiple phenotypes: limb-girdle muscular dystrophy, recessive type 2 (LGMDR2) 50% (26/52), proximodistal 15% (8/52), Miyoshi myopathy 8% (4/52), distal myopathy with anterior tibial onset (DMAT) 4% (2/52), and asymptomatic hyperCKemia 4% (2/52). In terms of molecular consequences (denominator = 48 unique variants), frameshift variants constituted 36% (17/48), missense variants 29% (14/48), nonsense variants 15% (7/48), splice donor variants 6% (3/48), splice acceptor variants 4% (2/48), intronic variants 2% (1/48), and synonymous variants 2% (1/48). Documenting these variants across populations facilitates diagnosis and informs future public health strategies. Notably, no cohort study based in Morocco has focused on the genetics of dysferlinopathy; existing Moroccan data are limited to isolated case reports.
Smaili et al. (Thu,) conducted a systematic review in Arab populations with genetic mutations in the DYSF gene associated with limb-girdle muscular dystrophy recessive type 2 (LGMDR2) and related myopathies. This systematic review identified a broad spectrum of pathogenic DYSF gene variants distributed across Arab populations from eight countries, with multiple recurrent and novel mutations associated with LGMDR2 and related myopathies.