A novel mutation in VRK1 associated with distal spinal muscular atrophy

J Hum Genet. 2019 Mar;64(3):215-219. doi: 10.1038/s10038-018-0553-5. Epub 2019 Jan 7.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Codon, Nonsense*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Muscular Atrophy, Spinal / genetics*
  • Pedigree
  • Phenotype
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics*

Substances

  • Codon, Nonsense
  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases
  • VRK1 protein, human