Identification of a DAGLB Mutation in a Non‐Chinese Patient with Parkinson's Disease

Abstract

Liu and colleagues 1 recently reported that biallelic mutations in DAGLB are responsible for autosomal recessive early-onset Parkinson's disease (AR-EO-PD). They first identified a homozygous DAGLB splice-site mutation in a consanguineous family with two affected siblings by combining homozygosity mapping and whole-exome sequencing. Through exome data mining in a large cohort of 1741 unrelated cases with PD, they identified three additional mutated index cases. All six patients were of Chinese origin and presented typical EO-PD (≤40 years) with a good response to levodopa. No additional cases outside of China have been reported so far.To assess the causal role of pathogenic variants in DAGLB in our French cohort, we used data mining in the exomes of 55 families with AR-PD (n = 88 cases) and 629 isolated EO-PD cases (Appendix S1). We identified a homozygous p.-Pro357Leu missense variant in a single consanguineous PD case (Fig. 1A). This mutation, predicted to be deleterious by 13 of 18 prediction software tested (Supporting Information Table S1 in Appendix S1), affects a conserved amino acid local-