1. Novel motor phenotypes in patients withVRK1mutations without pontocerebellar hypoplasia
- Author
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Garth A. Nicholson, Stephen R. Reddel, Michelle A. Farrar, Hugo Sampaio, Ying Zhu, James Cheng Yen Lee, Michael F. Buckley, Marion Stoll, Tony Roscioli, and Hooiling Teoh
- Subjects
Adult ,Male ,0301 basic medicine ,Pontocerebellar hypoplasia ,Protein Serine-Threonine Kinases ,Biology ,Compound heterozygosity ,medicine.disease_cause ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Family ,Age of Onset ,Motor Neuron Disease ,Exome sequencing ,Genetics ,Mutation ,Intracellular Signaling Peptides and Proteins ,Motor neuron ,SMA ,medicine.disease ,Phenotype ,Pedigree ,030104 developmental biology ,medicine.anatomical_structure ,Child, Preschool ,Female ,Neurology (clinical) ,Age of onset ,030217 neurology & neurosurgery - Abstract
Objective: To describe the phenotypes in 2 families with vaccinia-related kinase 1 ( VRK1 ) mutations including one novel VRK1 mutation. Methods: VRK1 mutations were found by whole exome sequencing in patients presenting with motor neuron disorders. Results: 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. Conclusions: VRK1 mutations can produce adult-onset SMA and motor neuron disease in children without pontocerebellar hypoplasia.
- Published
- 2016