No Alterations in et-Synuclein Gene Dosage Observed in Sporadic Parkinson's Disease

摘要

Berg and colleagues' have recently shown that a-synuclein (SNCA) point mutations seen in familial Parkinson's disease (PD) are rarely found in sporadic disease. In the last few years, it has become apparent that even in the absence of mutations detectable by sequence analysis, simple multiplications of SNCA can cause autosomal dominant forms of PD. Interestingly, there appears to be a dosage effect on clinical phenotype,with duplication of the gene resulting in a phenotype similar to idiopathic PD, but triplication resulting in early-onset par-kinsonism with dementia. In order to complement the efforts of Berg and colleagues, we sought to determine whether alterations in dosage of SNCA might account for a proportion of sporadic PD cases.We screened 538 PD patients and 923 controls for deletion or multiplication of SNCA. Cases included 160 patients involved in a community-based epidemiological study of incident PD and 378 consecutive prevalent cases attending our research clinic. All cases met UKPDS Brain Bank criteria for the diagnosis of PD. The mean age of disease onset was 63 years (range, 25-91); 2% of cases had early-onset disease (? 40 years); and 14% of cases reported a family history of one or more first-degree relatives with parkinsonian symptoms or tremor. Control individuals consisted of 146 spouses of PD cases and 777 parents of patients with multiple sclerosis (MS). Peripheral blood samples were collected following written informed consent and DNA was extracted using standard phenol/ chloroform methods.