Compound Heterozygous WARS2 Variants Including a Hypomorphic Allele Cause a Milder Phenotype of Complex Dopa Responsive Dystonia: Case Report and Review of the Literature.
Cerebellum
; 2024 Jul 29.
Article
em En
| MEDLINE
| ID: mdl-39073549
ABSTRACT
Biallelic WARS2 pathogenic variants responsible for partial defect in aminoacylation, have recently been reported in subjects presenting with late-onset phenotypes combining dopa-responsive early-onset dystonia parkinsonism with altered DaTSCAN and progressive myoclonus ataxia. Here, we present the case of a 39-year-old male with childhood-onset progressive dopa-responsive dystonia parkinsonism, prominent psychiatric features and ataxia whose genome sequencing identified a p.(Arg36Ter) nonsense variant and a hypomorphic p.(Trp13Gly) missense variant, allowing the diagnosis of WARS2-related disease. The p.(Trp13Gly) missense variant has previously been reported in individuals with less severe phenotypes than those carrying biallelic WARS2 loss-of-function variants. Among these individuals, two subjects had similar genetic backgrounds and almost identical clinical history to our patient. Our report brings additional proof that the p.(Trp13Gly) variant acts as a hypomorphic allele, offering insight on a genotype-phenotype correlation in WARS2-related disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cerebellum
Assunto da revista:
CEREBRO
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França