Motor Neurone Disease

Gene: VRK1

I don't know

PMID 34169149: expanding spectrum of neurologic disorders associated with VRK1. Two Hispanic individuals, one homozygous (R321C: VUS and LP/P in ClinVar) and one cHet (R321C+V236M, latter P and more recently VUS in ClinVar), with slowly progressive weakness and a clinical syndrome consistent with adult-onset spinal muscular atrophy WITHOUT pontocerebellar atrophy.

No hom in gnomAD and both have been reported in cHet individuals with other features: R321C in association with adult-onset amyotrophic lateral sclerosis and V236M with rapidly progressive sensorimotor polyneuropathy and microcephaly.

Authors suggest PMID 26583493 and 31837156 have similar reports. PMID 26583493 reports a 32yo Hispanic individual, cHet H119R+R321C, with early-onset amyotrophic lateral sclerosis, 5 years progressive weakness. PMID 31837156 reports two patients with adult-onset length-dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent, both hom for R387H.

Created: 2 Aug 2021, 6:58 a.m. | Last Modified: 2 Aug 2021, 6:58 a.m.

Panel Version: 0.123

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Adult-onset spinal muscular atrophy without pontocerebellar hypoplasia

Publications

• 34169149
• 26583493
• 31837156

Red List (low evidence)

The motor neuron disease reported in association with variants in this gene has been generally of childhood onset.

Created: 28 Sep 2020, 4:56 a.m. | Last Modified: 28 Sep 2020, 4:56 a.m.

Panel Version: 0.86

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Distal hereditary motor neuropathy; dHMN/dSMA

Publications

• 31560180
• 32242460
• 31178479
• 31837156
• 30847374

Comment on list classification: >3 independent cases with ALS/MND

Created: 18 Dec 2019, 7:32 a.m. | Last Modified: 18 Dec 2019, 7:32 a.m.

Panel Version: 0.30