Identification of a homozygous VRK1 mutation in two patients with adult-onset distal hereditary motor neuropathy

Background: Adult-onset hereditary motor neuropathies are caused by mutations in multiple genes. Mutations within the vaccinia-related kinase 1 (VRK1) gene were associated with a wide spectrum of recessively inherited motor neuropathies, characterized by childhood to early adulthood age of onset and an occasionally non-lower motor neuron involvement. Methods: We describe two patients with adult-onset (aged 48 and 40 years) length-dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent. One also demonstrated mild nocturnal respiratory difficulty and sensory symptoms. Whole-exome sequencing (WES) was performed. Results: A homozygous mutation in VRK1 (c.1160G>A (p.Arg387His)), shared by both patients, was identified. This rare mutation segregated with the disease in the two families, and was absent in 120 controls of Jewish Moroccan origin. Conclusions: Our findings support VRK1 as a causative gene for adult-onset distal hereditary motor neuropathy, and indicate its relevance for evaluation of individuals with similar motor impairment.