VRK1 variants in two Portuguese unrelated patients with childhood-onset motor neuron disease.
Amyotroph Lateral Scler Frontotemporal Degener
; 21(3-4): 291-295, 2020 05.
Article
in En
| MEDLINE
| ID: mdl-32242460
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Variation
/
Motor Neuron Disease
/
Protein Serine-Threonine Kinases
/
Intracellular Signaling Peptides and Proteins
Type of study:
Prognostic_studies
Limits:
Adult
/
Child
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
Amyotroph Lateral Scler Frontotemporal Degener
Year:
2020
Document type:
Article
Affiliation country:
Portugal