Genetic Screening for Two LRRK2 Mutations in French Patients with Idiopathic Parkinson's Disease

Abstract

Several pathogenic mutations in the LRRK2 gene have been implicated in familial and sporadic cases of Parkinson's disease (PD). We screened 103 sporadic French PD patients for the presence of the LRRK2 R1441G and G2019S mutations. The R1441G mutation was absent in our PD sporadic cases, but the G2019S mutation was present in 2 of them (1.9%). Clinical features in our 2 patients were not different from classic PD. One of our patients was of Berberian (North Africa) origin. Our 2 patients displayed genetic profiles consistent with the same ancestral haplotype as previously reported for carriers of the LRRK2 G2019S mutation.

Original Synthetic Report: Origin of the G2019S mutation associated to Parkinson’s disease in Europeans and in North Africans

“…The common haplotype associated with the G2019S mutation is shorter (in the sense that the length of the haplotype determined by variants at microsatellite polymorphisms is smaller in this patient, compared to that of the founder haplotype of the other French patient) in our French PD patient of Berberian origin (Funalot et al, 2006).…”

“…In our own study on sporadic French PD (Funalot et al, 2006) one of the two patients bearing the G2019S mutation is of Berberian origin. In Europe, the frequency of G2019S appears to be relatively high in northern Spain (Infante et al, 2006;Gaig et al, 2006;Mata et al, 2006) and Portugal (Bras et al, 2005;Ferreira et al, 2007), but low in northern Europe (Kachergus et al, 2005).…”

“…Thirteen European countries ( Figure 1) are concerned by our synthesis: Portugal (Bras et al, 2005;Ferreira et al, 2007), Spain (Infante et al, 2006;Gaig et al, 2006;Mata et al, 2006;Gao et al, 2009), Italy (Marongiu et al, 2006;Civitelli et al, 2007;Floris et al, 2009), France (Funalot et al, 2006), Austria (Haubenberger et al, 2007), Germany (Berg et al, 2005), Poland (Bialecka et al, 2005), England (Williams-Gray et al, 2006), Norway (Aasly et al, 2005), Sweden (Carmine Belin et al, 2006), Russia (Pchelina et al, 2006), Ukrainia (Illiarioshkin et al, 2007) and Greece (Spanaki et al, 2006;Kalinderi et al, 2007;Xiromerisiou et al, 2007) This synthesis totalizes a number of 5273 sporadic PD patients screened; seventy three (1.3%) of them are heterozygous for the mutation. Table 1 gives, for each location, 95% confidence intervals of the percentages according to the Poisson distribution.…”

Parkinson's disease in Arabs: A systematic review

“…Twenty nine published reports (dated 1986–2007) relating to PD in Arabs were identified, of which four case reports were excluded. The 25 reports included5–29 were classified as follows: genetic (n = 17), epidemiological (n = 3), and clinical series (n = 5).…”

New contribution on the <i>LRRK2</i> G2019S mutation associated to Parkinson’s disease: age estimation of a common founder event of old age in Moroccan Berbers

“…Genomic DNA was isolated from peripheral blood of patients and subjects using standard protocols; a signed informed consent was obtained by the concerned subjects. Detection of LRRK2 6055G > A (G2019S) mutation was performed as described previously (Funalot et al, 2006). Limited haplotype data on the two PD patients (one of them being of Berberian origin) and on the twenty-two subjects bearing the G2019S mutation (no individual homozygous) have been published elsewhere (Change et al, 2008); because of the instability of D12S2515, this marker was not taken in consideration in the present study (Zabetian et al, 2006a).…”