Investigators from Baylor College of Medicine, Texas Children's Hospital, Houston, TX; Kennedy Krieger Institute, Baltimore, MD; and University of Minnesota, MN, report 3 patients from 2 unrelated families with a complex neuropathy phenotype characterized by axonal sensorimotor neuropathy, severe nonprogressive microcephaly and cerebral dysgenesis. Compound heterozygous alleles responsible for the clinical phenotype were identified by whole-genome and whole-exome sequencing in 2 affected siblings from 1 family and a homozygous nonsense variant in the third unrelated patient in the vaccinia-related kinase 1 gene (VRK1). [1]
COMMENTARY. Hereditary motor and sensory neuropathies (HMSNs) are a group of slowly progressive diseases genetically heterogeneous, with more than 40 disease-associated genes identified. VRK1 is a novel HMSN locus that can be associated with a complex peripheral neuropathy phenotype, an autosomal recessive axonal motor sensory neuropathy and microcephaly. Genome-wide analysis enables the identification of novel HMSN-associated genes.