Research articleAutosomal dominant Parkinson's disease: Incidence of mutations in LRRK2, SNCA, VPS35 and GBA genes in Brazil

- This is the first molecular study in Brazilian index cases from families with ADPD.
- We screened specific mutations in LRRK2, SNCA, VPS35 and GBA genes.
- Heterozygous mutations in LRRK2 and GBA genes were found in 7.0% of the index cases.
- Our data reveal a substantial contribution of LRRK2 and GBA mutations to PD in Brazil.
- Our findings show that VPS35 and SNCA mutations are uncommon causes of PD in Brazil.

IntroductionAmongst Parkinson's disease (PD) genetic factors, mutations in LRRK2, SNCA, VPS35 and GBA genes are recognized causes of PD. Nonetheless, few genetic screenings have been conducted in families with a history of PD consistent with autosomal dominant inheritance (ADPD), and their relevance to the etiology of PD has been poorly explored in Latin American populations, such as the Brazilian one, with a high degree of admixture.MethodsIn order to assess the contribution of specific mutations in LRRK2, SNCA, VPS35 and GBA genes to ADPD in Brazil, we conducted the first molecular evaluation in a cohort of 141 index cases from families with ADPD. Genomic DNA was isolated from peripheral blood or saliva, and the molecular analysis was performed by TaqMan allelic discrimination assays or bidirectional sequencing.ResultsHeterozygous mutations in LRRK2 and GBA genes were identified in 10 (7.0%) probands, and all presented typical signs of classical PD. No mutations were found in SNCA or VPS35 genes.ConclusionOur findings in a representative series of index cases from families with ADPD emphasize the important contribution of LRRK2 G2019S and GBA (L444P and N370S) mutations to parkinsonism in Brazilian families. The absence of mutations in VPS35 and SNCA genes reveals that they are uncommon causes of PD in Brazil, corroborating previous studies that also failed to detect these genetic variants in PD patients from other populations. Recent discoveries of novel causative genes of autosomal dominant forms of PD expand the investigative possibilities and should be targeted on future studies.