Whole-exome sequencing reveals a rare interferon gamma receptor 1 mutation associated with myasthenia gravis

Abstract

Our study is aimed to explore the underlying genetic basis of myasthenia gravis. We collected a Chinese pedigree with myasthenia gravis, and whole-exome sequencing was performed on the two affected siblings and their parents. The candidate pathogenic gene was identified by bioinformatics filtering, which was further verified by Sanger sequencing. The homozygous mutation c.G40A (p.V14M) in interferon gamma receptor 1was identified. Moreover, the mutation was also detected in 3 cases of 44 sporadic myasthenia gravis patients. The p.V14M substitution in interferon gamma receptor 1 may affect the signal peptide function and the translocation on cell membrane, which could disrupt the binding of the ligand of interferon gamma and antibody production, contributing to myasthenia gravis susceptibility. We discovered that a rare variant c.G40A in interferon gamma receptor 1 potentially contributes to the myasthenia gravis pathogenesis. Further functional studies are needed to confirm the effect of the interferon gamma receptor 1 on the myasthenia gravis phenotype.

A Novel missense mutation of COL2A1 gene in a large family with stickler syndrome type I

“…A tiered filtering strategy was used to prioritize the SNVs and InDels using previously reported methods 16 . The obtained SNVs and InDels were further analysed for conservative and possible deleterious impact by software (dbNSFP version3.0).…”