Mutation analysis of the parkin and PINK1 genes in American Caucasian early-onset Parkinson disease families

Hao Deng, Weidong Le, Joohi Shahed, Wenjie Xie, Joseph Jankovic

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Mutations in the parkin gene and the PTEN-induced putative kinase 1 gene (PINK1) have been identified as the most common causes of autosomal recessive early-onset Parkinson disease (EOPD). To investigate the presence of the parkin and PINK1 gene mutation(s) and to explore genotype-phenotype correlations in American Caucasian families with EOPD from North American, we screened these two genes in probands of six families by direct sequencing, semi-quantitative PCR and RT-PCR. No PINK1 gene mutation was found in any of the probands, but compound heterozygous mutations (EX 3 del and EX 3_4 del) in the parkin gene were identified in one family. Extended analysis of the parkin-positive family showed the phenotype of patients was that of classic autosomal recessive EOPD, characterized by early age at onset, slow progression, beneficial response to levodopa, and levodopa-related motor complications. Three heterozygous mutation carriers (EX 3 del or EX 3_4 del) were free of any neurological symptoms. None of 62 healthy controls harbored EX 3 del or EX 3_4 del mutation. Our data suggest that compound heterozygous mutations (EX 3 and EX 3_4 del) in the parkin gene were the cause of EOPD in one of six Caucasian families; heterozygous EX 3 del and heterozygous EX 3_4 del forms were insufficient to cause this disorder, consistent with a loss-of-function mechanism of the parkin mutations. The results may provide new insights into the cause and diagnosis of PD and have implications for genetic counseling.

Original languageEnglish (US)
Pages (from-to)18-22
Number of pages5
JournalNeuroscience Letters
Volume430
Issue number1
DOIs
StatePublished - Jan 3 2008

Keywords

  • Early-onset Parkinson disease
  • Genetic counseling
  • Mutation
  • Parkin
  • PINK1

ASJC Scopus subject areas

  • Neuroscience(all)

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