Low frequency of common LRRK2 mutations in Mexican patients with Parkinson's disease

Mutations in leucine-rich repeat kinase 2 gene (LRRK2) account for as much as 5–6% of familial Parkinson's disease (PD) and 1–2% of sporadic PD. These mutations represent the most frequent cause of autosomal dominant PD, particularly in certain ethnic groups. In this first report concerning LRRK2 mutations in Mexican-mestizos, we screened 319 consecutive PD patients (186 males; 133 females; mean age at onset: 52.4 years) for LRRK2 mutations in exons 31 and 41 and for the mutation in exon 35, which produces the Y1699C substitution. Three (0.94%) patients, two with sporadic PD and one with familial PD (disease mean age at onset, 53.3 years), were heterozygous for LRRK2 mutations. Of these three, two patients had one of two different mutations in exon 31 (R1441G and R1441H, respectively); the other patient carried the G2019S mutation in exon 41. The Y1699C mutation was absent from this PD sample. Four additional subjects, unaffected relatives of one PD patient with a mutation in LRRK2, were subsequently genetically tested. None of the three LRRK2 mutations identified was present in 200 neurologically healthy Mexican control individuals. These findings have important implications for molecular testing of LRRK2 mutations in Mexican PD patients.

Research highlights▶ To our knowledge, this study represents the first analysis of LRRK2 mutations in PD patients and neurologically healthy controls of Mexican-mestizo ethnicity. ▶ The overall frequency (0.94%) of LRRK2 mutations in the 319 PD patients investigated is low. ▶ The R1441H mutation has been found in one patient. To the best of our knowledge, this is the first case of a Latin-American carrier.