Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
Neurobiol Aging. 2012 Apr;33(4):838.e1-5. doi: 10.1016/j.neurobiolaging.2011.10.032. Epub 2011 Dec 7.
Recently 2 groups have independently identified a mutation in the gene 'vacuolar protein sorting 35 homolog' (VPS35 c.1858G>A; p.Asp620Asn) as a possible cause of autosomal dominant Parkinson's disease (PD). In order to assess the frequency of the reported mutation and to search for other possible disease-causing variants in this gene, we sequenced all 17 exons of VPS35 in 96 familial PD cases, and exon 15 (in which the reported mutation is found) in an additional 64 familial PD cases, 175 young-onset PD cases, and 262 sporadic, neuropathologically confirmed PD cases. We identified 1 individual with the p.Asp620Asn mutation and an autosomal dominant family history of PD. Subsequent follow-up of the family confirmed an affected sibling and cousin who also carried the same mutation. No other potentially disease-causing mutations were identified. We conclude that the VPS35 c.1858G>A mutation is an uncommon cause of familial Parkinson's disease in our population.
最近有 2 组独立鉴定出基因“液泡蛋白分选 35 同源物”（VPS35 c.1858G>A；p.Asp620Asn）中的突变可能是常染色体显性帕金森病（PD）的一个原因。为了评估报道的突变的频率，并在该基因中寻找其他可能的致病变体，我们对 96 例家族性 PD 病例的 VPS35 的所有 17 个外显子以及另外 64 例家族性 PD 病例、175 例早发性 PD 病例和 262 例散发性、神经病理学确诊的 PD 病例的外显子 15（报道的突变发生在其中）进行了测序。我们发现了 1 例携带 p.Asp620Asn 突变的个体，以及 PD 的常染色体显性家族史。对该家族的后续随访证实了一名受影响的兄弟姐妹和表亲也携带相同的突变。未发现其他潜在的致病突变。我们的结论是，VPS35 c.1858G>A 突变在我们的人群中是家族性帕金森病的一个不常见原因。
