RESUMO
The recent discovery of mutations in Dardarin (LRRK2) have been related to the appearance of Parkinson's disease in several families. Notably, one single mutation in this gene (R1441G) not only appeared in familial, but also in apparently sporadic Parkinson disease (PD) patients of Basque descent. A clinical population was ascertained, and subjects were classified into Basque and non-Basque descent according to their known ancestry. The R1441G mutation was assayed using an allele-specific polymerase chain reaction, and several single nucleotide polymorphisms surrounding this mutation were analyzed by direct sequencing. In addition to 22 members of the original Basque families where R1441G was identified, we observed 17 carriers of the mutation who were apparently related through a common ancestor. From a clinical perspective, the disease observed in mutation carriers is indistinguishable from that in noncarriers. The R1441G mutation causes a form of Parkinson's disease that is equivalent to that observed in idiopathic Parkinson's disease. This mutation appears in 16.4% and 4.0% of familial and sporadic PD in this Basque population, respectively.
Assuntos
Arginina/genética , Cromossomos Humanos Par 12 , Glicina/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Idoso , Análise Mutacional de DNA , Demografia , Saúde da Família , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Espanha/epidemiologia , Espanha/etnologiaRESUMO
During the last few years several loci have been linked to Mendelian forms of Parkinson's disease (PD). To date, 5 causative genes of 10 identified loci are known, and they have provided enormous insight into the molecular pathways involved in this common neurodegenerative disorder. One of the recently identified loci, PARK8, causes autosomal dominant PD with, apparently, various degrees of abnormal deposition of alpha-synuclein or tau in the neuronal cells in the pedigrees currently reported. We genetically characterized four Basque families and found evidence for linkage of autosomal dominant PD to the PARK8 locus, with a maximum 2-point logarithm of odds score of 3.21 (theta = 0.00) for marker D12S345. The clinical features of these families are those of typical PD, including good response to levodopa therapy, rigidity, and akinesia, and a mean age of 55 years at disease onset.