RESUMEN
The spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders linked to more than 20 genetic loci. Most often, these diseases are caused by expansion of triplet repeats encoding polyglutamine (polyQ) tracts. The phenotype is variable and can cause a disease that overlaps clinically with Parkinson's disease (PD). l-Dopa-responsive parkinsonism with minimal cerebellar deficits has been described in SCA2 and SCA3. In order to define if mutation at these loci is a common cause of clinically defined parkinsonism we typed the SCA-2 and SCA-3 repeats for expansion in a series of 280 patients diagnosed with PD or parkinsonism. We identified one pathogenic expansion in SCA-2 in a North American family with autosomal dominant parkinsonism.
Asunto(s)
Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Adolescente , Anciano , Anciano de 80 o más Años , Ataxina-3 , Ataxinas , ADN/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares , Enfermedad de Parkinson/fisiopatología , Linaje , Secuencias Repetitivas de Ácidos Nucleicos/genética , Proteínas Represoras , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Temblor/fisiopatologíaRESUMEN
BACKGROUND: Mutations in the PTEN-induced kinase (PINK1) gene located within the PARK6 locus on chromosome 1p35-p36 have recently been identified in patients with recessive early-onset Parkinson disease. OBJECTIVE: To assess the prevalence of PINK1 mutations within a series of early- and late-onset Parkinson disease patients living in North America. DESIGN: All coding exons of the PINK1 gene were sequenced in a series of 289 Parkinson disease patients and 80 neurologically normal control subjects; the mutation frequencies were evaluated in additional controls (100 white and 50 Filipino subjects). RESULTS: We identified 27 variants, including the first reported compound heterozygous mutation (Glu240Lys and Leu489Pro) and a homozygous Leu347Pro mutation in 2 unrelated young-onset Parkinson disease patients. CONCLUSION: Autosomal recessive mutations in PINK1 are a rare cause of young-onset Parkinson disease.