A novel mutation in VRK1 associated with distal spinal muscular atrophy

Distal spinal muscular atrophy (dSMA) is a rare clinically and genetically heterogeneous group of inherited disorders characterized by progressive distal muscle weakness and wasting. So far, more than 65% of patients with dSMA have undiscovered genetic mutations. Recently, compound heterozygous mutations in the vaccinia-related kinase 1 (VRK1) gene have been identified for the first time in two siblings with adult-onset dSMA from an Ashkenazi Jewish family. Here, we also report two affected siblings with adult-onset dSMA in a Chinese family. Whole exome sequencing and subsequent Sanger sequencing identified a novel nonsense mutation (c.1124G >A, p.W375*) in exon 12 of the VRK1 gene, co-segregating with the dSMA phenotype in an autosomal recessive pattern. In conclusion, our findings identify a novel nonsense mutation p.W375* in the VRK1 gene in a Chinese family with autosomal recessive dSMA and broaden the genetic spectrum of VRK1-associated dSMA.