The genetics of Parkinson disease: to test or not to test.

The LRRK 2 gene is a very large gene consisting of 51 exons, with pathological mutations reported to date in 10 of the exons. The most common mutation is G2019S, located in exon 41. The frequency of this mutation varies among different ethnic groups, with the highest frequency found in PD patients from Northern Africa, including the Arabic (30%) and Ashkenazy Jewish (18%) populations. It has been postulated that the founder mutation (the same one for both populations) occurred over 3,000 years ago. This mutation is much less common in the Northern European populations. Up to 1% of patients with early onset PD carry this gene. Thus, based on population data, it appears that the two most common involved loci in familial and sporadic PD are the genes for Parkin and LRRK 2. Until very recently, genetic testing was only available in research laboratories under research protocols, but has now become available as a service in the U.S. Should testing be routinely available in Canada? Several general issues need to be considered: 1) If individuals are confirmed to have a mutated gene, treatment remains the same. There is no neuroprotective therapy or impact on management. 2) Penetrance is decreased in LRRK 2, that is, not everyone who has this gene will develop symptoms. Alternatively, some individuals may be quite elderly before showing symptoms. Thus, clinical correlation can be difficult to determine. 3) Only the more common mutations can be easily identified. Sequencing of the whole gene to identify less common mutations is very expensive and time consuming. 4) As these two genetic loci still represent a minority of PD cases, cost-effectiveness of testing would be low. 4) Heterozygote carriers of the Parkin mutation are not uncommon. However, significant controversy exists on whether this translates to a predisposition for developing PD (recent evidence suggests not). 5) Psychosocial effects of testing in the PD population are unknown. The two papers in this issue of the Journal address the issue of whether LRRK2 is a cause of PD in the Canadian population with emphasis on French Canadians. A total of 335 patients with PD from Ontario and Quebec were screened; of these, the majority (252) were drawn from the French Canadian population. 5,6 Both papers conclude that the common mutation (G2019S) is not present in this population. Dupre et al 5 additionally screened exon 31, while Grimes et al 6 screened a total …