In a cohort of 961 clinically suspected Duchenne muscular dystrophy patients, 105 were diagnosed to have other muscular dystrophies (OMDs), with LGMD2E (variant SGCB c.544A>C) being the most common

Abstract

Abstract Background Targeted next generation sequence analyses in a cohort of 961 previously described patients with clinically suspected Duchene muscular dystrophy (DMD) revealed that 145/961 (15%) had variants in genes associated with other muscular dystrophies (OMDs). Methods NGS was carried out in DMD negative patients after deletion/duplication analysis followed by WES for No variant cases. Results The majority of patients with OMDs had autosomal recessive diseases that included Limb‐Girdle Muscular Dystrophies (LGMDs), Bethlem, Ullrich congenital Myopathies and Emery‐Driefuss muscular dystrophy. 3.5% of patients were identified with other disorders like Charcot‐Marie Tooth and Nemaline myopathy. A small percentage of patients, 0.6% remain undiagnosed. Of a total of 78 genetic variants identified, 44 were found to be novel. Interestingly, a third of patients with OMDs were found to have LGMD2E/R4, a severe form of LGMD that afflicts young children with clinical symptoms similar to DMD. Almost one third of the unrelated LGMD2E/R4 patients had the same point mutation (c.544A>C) in the SGCB gene, suggestive of a founder effect, described here for the first time in India. Conclusion This study underscores the need for a complete genetic work up to precisely diagnose patients and to initiate appropriate counseling programs, disease management and prevention strategies.

Keywords

• autosomal recessive disorder
• Duchenne muscular dystrophy
• limb girdle muscular dystrophy 2E‐R4
• muscular dystrophy
• next generation sequencing
• overlapping symptoms