Compound Heterozygous WARS2 Variants Including a Hypomorphic Allele Cause a Milder Phenotype of Complex Dopa Responsive Dystonia: Case Report and Review of the Literature.

Fiche publication

Date publication

juillet 2024

Journal

Cerebellum (London, England)

Auteurs

Membres identifiés du Cancéropôle Est :
Pr THAUVIN-ROBINET Christel

Tous les auteurs :
Schneider V, Dupont G, Madinier G, Ramond F, Lesca G, Thauvin-Robinet C, Thomas Q

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/39073549

Résumé

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.