Department. of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research and DZNE- German Center for Neurodegenerative Diseases, Tübingen, Hoppe-Seyler-Str. 3, Tübingen 72076, Germany.
J Med Genet. 2012 Nov;49(11):721-6. doi: 10.1136/jmedgenet-2012-101155.
Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive.
We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort.
Our study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.
最近的两项研究发现，液泡蛋白分选 35 基因中的突变（p.Asp620Asn）是常染色体显性遗传帕金森病的一个原因。尽管描述了其他错义变异，但它们的致病性仍不确定。
我们进行了最大的多中心研究，以确定在全球超过 15000 个人中报道的液泡蛋白分选 35 基因突变的频率和致病性。p.Asp620Asn 在 5 个家族性和 2 个散发性 PD 病例中被检测到，而在健康对照组中未被检测到，p.Leu774Met 在 6 个病例和 1 个对照组中被检测到，p.Gly51Ser 在 3 个病例和 2 个对照组中被检测到。总体分析未发现我们队列中 p.Leu774Met 和 p.Gly51Ser 有任何显著的风险增加。
除了在家族性病例中发现 p.Asp620Asn 变异外，我们的研究还在特发性帕金森病病例中发现了该变异，从而为 p.Asp620Asn 在世界各地不同人群中的帕金森病中的作用提供了遗传证据。
