Levodopa-responsive dystonia caused by biallelic PRKN exon inversion invisible to exome sequencing.

ABSTRACT: Biallelic pathogenic variants in PRKN (PARK2), encoding the E3 ubiquitin ligase parkin, lead to early-onset Parkinson's disease. Structural variants, including duplications or deletions, are common in PRKN due to their location within the fragile site FRA6E. These variants are readily detectable by copy number variation analysis. We studied four siblings with levodopa-responsive dystonia by exome sequencing followed by genome sequencing. Affected individuals developed juvenile levodopa-responsive dystonia with subsequent appearance of parkinsonism and motor fluctuations that improved by subthalamic stimulation. Exome sequencing and copy number variation analysis were not diagnostic, yet revealed a shared homozygous block including PRKN. Genome sequencing reveale

SUBMITTER: Mor-Shaked H 

PROVIDER: S-EPMC8421701 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature