两同胞均患有典型帕金森病，其 SYNJ1 基因存在新型纯合突变。
A novel homozygous SYNJ1 mutation in two siblings with typical Parkinson's disease.
机构信息
Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
出版信息
Parkinsonism Relat Disord. 2019 Dec;69:134-137. doi: 10.1016/j.parkreldis.2019.11.001. Epub 2019 Nov 5.
BACKGROUND
Mutations in the SYNJ1 have been associated with early onset of atypical Parkinson's disease (PARK20). Patients with PARK20 exhibit a wide phenotypic variability. Here, we report the clinical and genetic findings in two affected siblings with a novel homozygous SYNJ1 mutation.
METHODS
A consanguineous family with two affected siblings with Parkinson's disease was recruited. Both siblings underwent detailed neurological examinations. Whole genome sequencing was performed in the proband.
RESULTS
Both affected siblings presented with pure parkinsonism with no other atypical symptoms and a slow disease progression. The proband had an excellent response to levodopa. Performing the levodopa challenge test in the proband's older brother resulted in improvements in the parkinsonism signs. Genetic analysis identified a homozygous missense mutation in SYNJ1 (c.2495A > G, p.Y832C) in both of siblings. In silico analyses revealed that the mutation was deleterious.
CONCLUSIONS
Screening for SNYJ1 should be considered in patients with typical levodopa-responsive Parkinson's disease.
背景
SYNJ1 突变与早发性非典型帕金森病（PARK20）有关。PARK20 患者表现出广泛的表型变异性。在这里，我们报告了一对受影响的同卵双胞胎的临床和遗传发现，他们携带一种新的纯合 SYNJ1 突变。
方法
我们招募了一个患有帕金森病的同卵双胞胎家庭。这对双胞胎都接受了详细的神经学检查。对先证者进行了全基因组测序。
结果
这对受影响的双胞胎均表现为单纯的帕金森病，无其他非典型症状，且疾病进展缓慢。先证者对左旋多巴有很好的反应。在先证者的哥哥中进行左旋多巴挑战测试导致帕金森病症状改善。基因分析在这对双胞胎中均发现了 SYNJ1 的纯合错义突变（c.2495A>G，p.Y832C）。计算机分析显示该突变具有有害性。
结论
对于对左旋多巴反应良好的典型帕金森病患者，应考虑进行 SNYJ1 筛查。
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