Compound Heterozygous Variants of GOSR2 Associated With Congenital Muscular Dystrophy and Progressive Myoclonus Epilepsy

Objectives The GOSR2 gene is a Golgi vesicle transport gene that encodes for the Golgi SNAP receptor complex member 2 protein. This protein mediates transport between the medial and trans-Golgi compartments. The homozygous missense variant in the GOSR2 gene, c.430G>T, has been associated with progressive myoclonus epilepsy (PME). There have been reports suggesting that compound heterozygous GOSR2 variants are associated with the congenital muscular dystrophy (CMD) phenotype. Methods In this article, we report a pediatric case with congenital hypotonia, motor delay, elevated creatine kinase, and abnormal muscle biopsy consistent with CMD who subsequently developed PME. Whole-exome sequencing identified pathogenic compound heterozygous variants in the GOSR2 gene, one of which was the previously described PME-related c.430G>T(p.Gly144Trp), and a novel variant, c.22dup(p.Thr8fs). Result To our knowledge, this is a novel case of compound heterozygous variants in GOSR2 associated with both CMD and PME phenotypes. Discussion This case adds to the expanding clinical phenotype of GOSR2-related neurologic diseases.