Luo_2025_J.Neural.Transm.(Vienna)__

Hereditary factors play a significant role in the development of Parkinson's disease and the identification of causative genes is ongoing. Biallelic variants in Diacylglycerol lipase beta (DAGLB) are related to early-onset Parkinson's disease (EOPD) in the Chinese population, and have also been identified in an Algerian case. To date, no EOPD cases with DAGLB variants have been reported among Japanese patients. This study was conducted to clarify the occurrence of DAGLB variants among Japanese EOPD patients. We screened 270 patients with sporadic EOPD (male: female ratio, 1.37:1; mean age at onset +/- standard deviation, 37.32 +/- 7.91 years), and 276 patients with suspected autosomal recessive Parkinson's disease (ARPD, male: female ratio, 0.75:1; mean age at onset +/- standard deviation, 58.86 +/- 14.67 years). Genetic screening of all coding exons and flanking splicing regions was performed by Sanger sequencing. We identified two rare biallelic variants in two patients, both from consanguineous families. One variant was a homozygous frameshift variant (c.1770_1771del, p.Tyr591ProfsTer26), which was predicted to be pathogenic. The other was a missense variant (c.1444T > C, p.Tyr482His) and was predicted to be benign, with co-segregation ruled out for this variant. We identified a pathogenic variant in the DAGLB gene. Together with previous reports, these findings provide further evidence that loss-of-function variants in DAGLB are involved in EOPD in the Japanese population.