Molecular diagnosis of Alpha-sarcoglycanopathies by NGS in seven Moroccan families and report of two novel variants.

backgroundLimb-girdle muscular dystrophies constitute a heterogeneous group of neuromuscular diseases, both clinically and genetically. Limb-girdle muscular dystrophy by alpha-sarcoglycan deficiency or LGMD R3 α-sarcoglycan-related is a subtype of the autosomal recessive sarcoglycanopathies caused by variants in the alpha-sarcoglycan gene (SGCA) at 17q21.33. It appears in childhood by progressive weakness of pelvic and/or scapular girdle muscles and calf hypertrophy, with a wide range of clinical inter- and intra-familial clinical variability.

aimsOur report extends the molecular spectrum of SGCA gene with the identification of variant disease causing and will help for better management of patients and genetic counseling of families.

methodsIn our study, seven unrelated families presented a clinical and paraclinical picture consistent with alpha-sarcoglycanopathy. A molecular study using Next-Generation Sequencing (NGS) was carried out on them.

resultsSix different homozygous variants of the SGCA gene were identified in the patients analyzed, including four previously reported variants and two novel variants predicted to be deleterious by the prediction tools.

conclusionsOur results expand the spectrum of variants in Moroccan patients with sarcoglycanopathy, specifically LGMDR3, most importantly as this form is not common in the Moroccan population.