Novel motor phenotypes in patients with VRK1 mutations without pontocerebellar hypoplasia.

Abstract

To describe the phenotypes in 2 families with vaccinia-related kinase 1 (VRK1) mutations including one novel VRK1 mutation. VRK1 mutations were found by whole exome sequencing in patients presenting with motor neuron disorders. We identified pathogenic mutations in the VRK1 gene in the affected members of 2 families. In family 1, compound heterozygous mutations were identified in VRK1, c.356A>G; p.H119R, and c.1072C>T; p.R358*, in 2 siblings with adult onset distal spinal muscular atrophy (SMA). In family 2, a novel VRK1 mutation, c.403G>A; p.G135R and c.583T>G; p.L195V, were identified in a child with motor neuron disease. VRK1 mutations can produce adult-onset SMA and motor neuron disease in children without pontocerebellar hypoplasia.