Identification of a homozygous VRK1 mutation in two patients with adult‐onset distal hereditary motor neuropathy. Issue 3 (16th January 2020)

• Record Type: Journal Article
• Authors: Greenbaum, Lior; Barel, Ortal; Nikitin, Vera; Hersalis‐Eldar, Adi; Kol, Nitzan; Reznik‐Wolf, Haike; Dominissini, Dan; Pras, Elon; Dori, Amir
• Is Part Of: Muscle & nerve. Volume 61:Issue 3(2020)
• Page Start: 395
• Page End: 400
• Publication Date: 2020-01-16
• Subjects: distal hereditary motor neuropathy -- distal spinal muscular atrophy -- adult‐onset neuropathy -- VRK1 -- whole‐exome sequencing; Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.26779
• Languages: English
• ISSNs: 0148-639X

Abstract

Abstract: Background: Adult‐onset hereditary motor neuropathies are caused by mutations in multiple genes. Mutations within the vaccinia‐related kinase 1 ( VRK1 ) gene were associated with a wide spectrum of recessively inherited motor neuropathies, characterized by childhood to early adulthood age of onset and an occasionally non‐lower motor neuron involvement. Methods: We describe two patients with adult‐onset (aged 48 and 40 years) length‐dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent. One also demonstrated mild nocturnal respiratory difficulty and sensory symptoms. Whole‐exome sequencing (WES) was performed. Results: A homozygous mutation in VRK1 (c.1160G>A (p.Arg387His)), shared by both patients, was identified. This rare mutation segregated with the disease in the two families, and was absent in 120 controls of Jewish Moroccan origin. Conclusions: Our findings support VRK1 as a causative gene for adult‐onset distal hereditary motor neuropathy, and indicate its relevance for evaluation of individuals with similar motor impairment.