Luo Yue, Funayama Manabu, Hatano Taku, Li Yuanzhe, Yoshino Hiroyo, Yamashita Satoshi, Mori Akira, Nakamura Ryoichi, Hashizume Yoshio, Yoshida Mari, Riku Yuichi, Kanzato Naomi, Hattori Nobutaka
Department of Neurology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
J Neural Transm (Vienna). 2025 Apr 17. doi: 10.1007/s00702-025-02926-y.
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 β (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.
遗传因素在帕金森病的发病过程中起着重要作用，目前对致病基因的鉴定工作仍在进行。二酰基甘油脂肪酶β（DAGLB）的双等位基因变异与中国人群早发性帕金森病（EOPD）相关，在1例阿尔及利亚病例中也已得到确认。迄今为止，日本患者中尚未有DAGLB变异的EOPD病例报道。本研究旨在明确日本EOPD患者中DAGLB变异的发生情况。我们筛查了270例散发性EOPD患者（男:女比例为1.37:1；发病时平均年龄±标准差为37.32±7.91岁）以及276例疑似常染色体隐性帕金森病（ARPD）患者（男:女比例为0.75:1；发病时平均年龄±标准差为58.86±14.67岁）。通过桑格测序对所有编码外显子和侧翼剪接区域进行基因筛查。我们在2例患者中鉴定出2种罕见的双等位基因变异，这2例患者均来自近亲家庭。其中1种变异为纯合移码变异（c.1770_1771del，p.Tyr591ProfsTer26），预测具有致病性。另一种为错义变异（c.1444T>C，p.Tyr482His）且预测为良性，该变异的共分离情况已被排除。我们在DAGLB基因中鉴定出1种致病变异。结合之前的报道，这些发现进一步证明DAGLB功能丧失变异与日本人群的EOPD有关。
