三名奥地利帕金森病患者的UQCRC1基因中存在一种罕见变异，即p.(Gly405Val)。
A rare variant in the UQCRC1 gene, p.(Gly405Val) in three Austrian Parkinson's patients.
作者信息
Brücke Christof, Brücke Thomas, Pirker Walter, Zimprich Alexander
机构信息
Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences & Mental Health, Medical University of Vienna, Vienna, Austria.
Sigmund Freud University, Vienna, Austria.
出版信息
Parkinsonism Relat Disord. 2025 Feb;131:107250. doi: 10.1016/j.parkreldis.2024.107250. Epub 2024 Dec 21.
BACKGROUND
Variants in the UQCRC1 gene have been proposed to cause autosomal dominant Parkinson's disease with neuropathy. However, definitive confirmation of UQCRC1 as an authentic Parkinson's gene remains elusive, as follow-up studies have not yet provided conclusive evidence.
METHODS
382 Austrian Parkinson's patients, particularly selected for familial and/or early onset cases, were Exome sequenced.
RESULTS
We found three unrelated patients with a positive family history of the disease who shared the same rare missense variant in the UQCRC1 gene: c.1214G > T; p.(Gly405Val). The variant is very rare in the control population, with an allele frequency of 2 × 10 in the gnomAD database. None of the three patients carries a rare variant in a monogenic Parkinson's disease gene.
CONCLUSION
We suggest that UQCRC1 p.(Gly405Val) probably contributes to the development of the disease in these three patients. Our findings provide further evidence that UQCRC1 is a 'bona fide' Parkinson's disease gene.
背景
已有研究提出，UQCRC1基因变异可导致常染色体显性遗传性帕金森病伴发神经病变。然而，由于后续研究尚未提供确凿证据，UQCRC1作为帕金森病真正致病基因的最终确认仍未实现。
方法
对382例奥地利帕金森病患者进行外显子测序，这些患者是特意挑选出的家族性和/或早发性病例。
结果
我们发现3例有帕金森病家族史的非亲缘患者，他们在UQCRC1基因中共享相同的罕见错义变异：c.1214G>T；p.(Gly405Val)。该变异在对照人群中非常罕见，在gnomAD数据库中的等位基因频率为2×10。这3例患者均未携带单基因帕金森病基因的罕见变异。
结论
我们认为，UQCRC1 p.(Gly405Val)可能促使这3例患者发病。我们的研究结果进一步证明UQCRC1是一种“真正的”帕金森病基因。
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