Congenital Myasthenic Syndrome: Spectrum of Mutations in an Indian Cohort.

OBJECTIVES

To investigate the mutational spectrum and genotype-phenotype correlation in Indian patients with congenital myasthenic syndrome (CMS), using next-generation sequencing of 5 genes.

METHODS

CHRNE, COLQ, DOK7, RAPSN, and GFPT1 were sequenced in 25 affected patients.

RESULTS

We found clinically significant variants in 18 patients, of which variants in CHRNE were the most common, and 9 were novel. A common pathogenic COLQ variant was also detected in 4 patients with isolated limb-girdle congenital myasthenia.

CONCLUSIONS

Targeted screening of 5 genes is an effective alternate test for CMS, and an affordable one even in a developing country such as India. In addition, we recommend that patients with isolated limb-girdle congenital myasthenia be screened initially for the common COLQ pathogenic variant. This study throws the first light on the genetic landscape of CMSs in India.