Screening PARK genes for mutations in early-onset Parkinson's disease patients from Queensland, Australia
Introduction
Parkinson's disease (PD) is a neurodegenerative condition with a typical onset in the seventh decade, however, about 4% of PD patients present with early-onset before the age of 50 years [1]. It is a complex, multifactorial disorder, comprising genetic and environmental components. The majority of cases appear to be sporadic or idiopathic, however, in the recent past a number of mutations in at least six genes (PARK1, 2, 5, 6, 7, and 8) have been identified as being causative in the familial form of the condition, accounting for a small number of all PD cases. Mutations in these genes may lead to the disease phenotype and are often characterized by an earlier onset (under the age of 50 years) with or without Lewy body pathology. It is to be expected that more mutations causative for the disease in ‘sporadic’ PD will be identified in the future, adding to the number of distinct genetic forms of PD. The aetiology of the sporadic form of PD is still unclear but identification of molecular mechanisms and gene products underlying the disease in its monogenic form have shed some light on possible pathways involved in the non-hereditary form of the condition.
As an early disease onset is frequent in familial PD, we undertook in this study to estimate the prevalence of known genetic forms of Parkinsonism in a typical Australian population (Queensland) by screening a subset of early-onset cases, derived from a large movement disorders clinic in Brisbane, Australia.
Section snippets
Sampling frame
Patients were derived from a case series of 950 patients with a diagnosis of PD seen in one specialist movement disorders practice in Brisbane, between 2000 and 2005. Informed consent was obtained from all participating patients.
Patient selection
Patients were included in the study if they (1) received a diagnosis of probable PD according to stringent clinical and neurological criteria; (2) exhibited onset of symptoms ≤50 years; and (3) had been seen at the clinic between 2001 and 2005.
Patient ethnicity
Patients in this sample
Results
Seventy-four patients met the inclusion criteria. Demographic data are shown in Table 2. In this sample, males were slightly over-represented (n = 44, 59.5%). A self-reported family history of PD existed for 30 patients (40.5%). Of these, 13 each had a first- or a second-degree relative with PD and four patients reported a more distant relative affected by the condition. Among the first-degree relatives, there were six affected fathers and four affected mothers. More specific unambiguous
Discussion
The importance of genetic factors for the aetiology of PD has been debated controversially for a long time. Longitudinal twin studies argued for a genetic element contributing to the condition whereas other cross-sectional studies could find no evidence for inheritance [4], [5]. In the meantime, at least five genes have been identified that are implicated in the development of a monogenic form of PD (PARK1, 2, 6, 7, and 8). These monogenic forms of the condition may mimic clinically sporadic PD
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