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CMT2 and distal hereditary motor neuropathy associated with VRK1 variants: Case series

Sasha A Živković1, Richard J Nowak2, Daniel DiCapua2

  • 1Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; CMT Program at Yale University, Department of Neurology, Yale University, New Haven, CT, USA.

Neuromuscular Disorders : NMD
|December 18, 2024
PubMed

Insights

Vaccinia-related kinase 1 (VRK1) gene variants are linked to rare neuromuscular disorders like Charcot-Marie-Tooth disease (CMT2) and distal hereditary motor neuropathy (dHMN). This study details three cases, expanding the known clinical spectrum of VRK1-associated conditions.

Area of Science:

  • Genetics and Molecular Biology
  • Neurology
  • Biochemistry

Background:

  • Axonal Charcot-Marie-Tooth disease (CMT2) and distal hereditary motor neuropathy (dHMN) involve genes regulating axonal transport, RNA metabolism, mitochondrial dynamics, and DNA repair.
  • VRK1 (vaccinia-related kinase 1) is a kinase crucial for RNA processing and DNA damage response, with known links to neurodevelopmental and neuromuscular disorders.

Observation:

  • Three cases of VRK1-associated neuromuscular disorders without neurodevelopmental abnormalities are presented.
  • Case 1: CMT2 with a homozygous VRK1 variant (Arg387His).
  • Case 2 & 3: dHMN with compound heterozygous VRK1 variants (Arg133His and Asp243Asn).

Findings:

  • This case series expands the clinical spectrum of VRK1-associated neuromuscular disorders.
  • Identified specific VRK1 variants (Arg387His, Arg133His, Asp243Asn) linked to CMT2 and dHMN.
  • Demonstrated VRK1 variants can cause neuromuscular disorders without neurodevelopmental deficits.

Implications:

  • Further research is needed to understand the pathophysiology of VRK1-related neuromuscular disorders.
  • Highlights VRK1 as a significant gene in the etiology of inherited neuropathies.
  • Suggests genetic testing for VRK1 variants in patients with unexplained CMT2 or dHMN.
Keywords:
CMT2Distal hereditary motor neuropathyNeurodevelopmental disordersPontocerebellar hypoplasiaVRK1

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