VRK1 variants in two Portuguese unrelated patients with childhood-onset motor neuron disease

Abstract

VRK1 encodes a serine/protein kinase possibly involved in pathways related to amyotrophic lateral sclerosis (ALS) pathogenesis. Pathogenic variants in VRK1 have been related to different phenotypes. We describe the clinical phenotype of two unrelated Portuguese patients with different VRK1 variants. Both patients presented a bilateral distal weakness in lower limbs beginning in childhood slowly progressing to upper limbs, associated with pyramidal signs, without bulbar, respiratory or cognitive involvement, according to probable ALS. Imaging and nerve conduction studies were unremarkable in both patients. Genetic testing in patient 1 identified two VRK1 variants in heterozygosity: c.265C > T, p.(Arg89*) and c.769G > A, p.(Gly257Ser), classified as pathogenic and variant of uncertain significance, respectively. In patient 2, two probably pathogenic variants in VRK1 were identified in heterozygosity: c.710-14T > C in intron 8 and c.721C > T, p.(Arg241Cys) in exon 9. We report two unrelated patients with different variants in VRK1 displaying a similar childhood-onset motor neuron disease/ALS, further expanding the phenotypic spectrum associated to VRK1 variants.

Keywords:

• Amyotrophic lateral sclerosis
• childhood-onset
• hereditary
• motor neuron disease
• VRK1

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Informed consent

Both patients have signed an informed consent for genetic testing.

Additional information

Funding

This work was funded by the project Comprehensive evaluation of circulating MicroRNA as diagnostic and prognostic biomarkers in Amyotrophic Lateral Sclerosis [PTDC/MEC-NEU/31195/2017].