Mutations in the LRRK2 and GBA genes are increasingly recognized as frequent determinants of familial and sporadic Parkinson's disease (PD). However, for several populations, accurate data on the prevalence and types of mutations are not available, because previous studies have not investigated the complete coding regions of these genes in large samples. We studied 312 PD patients ascertained at a single centre in Lisbon, Portugal. In 61 patients, with familial PD, we sequenced the entire open reading frames and exon-intron boundaries of LRRK2 and GBA. In LRRK2, we identified ten heterozygous p.Gly2019Ser (16.4%), and two heterozygous p.Arg1441His carriers (3.3%); furthermore, six patients each carried a novel LRRK2 heterozygous variant (five coding and one 3'-UTR variants) of undetermined pathogenic role. Segregation of the p.Arg1441His mutation with PD was observed in the families of both carriers. None of these variants were identified in 138 healthy controls. Screening of GBA revealed no mutations. In the remaining 251 PD patients (25 familial and 226 sporadic) we found ten additional carriers of the heterozygous p.Gly2019Ser and no carriers of the other mutations. Thus, the p.Gly2019Ser mutation was detected in a total number of 20 carriers out of 312 patients (6.4%), including twelve familial (14%) and eight sporadic patients (3.5%).This comprehensive study confirms that p.Gly2019Ser is the most important genetic cause of PD known so far in Portugal and supports the contention that p.Arg1441His is also a PD-causing mutation. These findings have relevance for the genetic testing and counseling of PD patients in this population.

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doi.org/10.1016/j.parkreldis.2013.05.003, hdl.handle.net/1765/41350
Parkinsonism & Related Disorders
Erasmus MC: University Medical Center Rotterdam

Zhang, L, Quadri, M, Guedes, L.C, Coelho, M, Valadas, A, Mestre, T, … Bonifati, V. (2013). Comprehensive LRRK2 and GBA screening in Portuguese patients with Parkinson's disease: Identification of a new family with the LRRK2 p.Arg1441His mutation and novel missense variants. Parkinsonism & Related Disorders, 19(10), 897–900. doi:10.1016/j.parkreldis.2013.05.003