A novel VRK1 mutation associated with recessive distal hereditary motor neuropathy

Vaccinia‐related kinase 1 (VRK1) mutations can cause motor phenotypes including axonal sensorimotor neuropathy, distal hereditary motor neuropathy (dHMN), spinal muscular atrophy, and amyotrophic lateral sclerosis. Here, we identify a novel homozygous VRK1 p.W375X mutation causing recessive dHMN. The proband presented with juvenile onset of weakness in the distal lower extremities, slowly progressing to the distal upper limbs, with bilateral pes cavus and no upper motor or sensory neuron involvement. Nerve conduction studies showed a pure motor axonal neuropathy. Our findings extend the ethnic distribution of VRK1 mutations, indicating that these mutations should be included in genetic diagnostic testing for dHMN.

[1]  V. Ramesh,et al.  Genetic heterogeneity of motor neuropathies , 2017, Neurology.

[2]  T. Roscioli,et al.  Novel motor phenotypes in patients with VRK1 mutations without pontocerebellar hypoplasia , 2016, Neurology.

[3]  W. Wiszniewski,et al.  Expanding Phenotype of VRK1 Mutations in Motor Neuron Disease , 2015, Journal of clinical neuromuscular disease.

[4]  K. Xia,et al.  A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy , 2015, Neurology.

[5]  Bale,et al.  Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology , 2015, Genetics in Medicine.

[6]  J. Lupski,et al.  Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly. , 2013, JAMA neurology.

[7]  D. Lambrechts,et al.  Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motor neuropathy , 2013, European Journal of Human Genetics.

[8]  S. Blumen,et al.  A rare recessive distal hereditary motor neuropathy with HSJ1 chaperone mutation , 2012, Annals of neurology.

[9]  B. Kalmar,et al.  The distal hereditary motor neuropathies , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[10]  Wei Chen,et al.  Deep sequencing reveals 50 novel genes for recessive cognitive disorders , 2011, Nature.

[11]  M. King,et al.  Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. , 2009, American journal of human genetics.

[12]  N. Wood,et al.  Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2 , 2008, Neurology.

[13]  A. Munnich,et al.  The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset. , 2007, American journal of human genetics.