Molecular genetic analysis of a novel <i>Parkin</i> gene in Japanese families with autosomal recessive juvenile parkinsonism: Evidence for variable homozygous deletions in the <i>Parkin</i> gene in affected individuals

DOI Web Site Web Site 被引用文献25件

抄録

<jats:title>Abstract</jats:title><jats:p>Autosomal recessive juvenile parkinsonism (AR‐JP) is a distinct clinical and genetic entity characterized by selective degeneration of nigral dopaminergic neurons and young‐onset parkinsonism with remarkable response to levodopa. Recently, we mapped the gene locus for AR‐JP to chromosome 6q25.2–q27 by linkage analysis and we identified a novel large gene, <jats:italic>Parkin</jats:italic>, consisting of 12 exons from this region; mutations of this gene were found to be the cause of AR‐JP in two families. Now we report results of extensive molecular analysis on 34 affected individuals from 18 unrelated families with AR‐JP. We found four different homozygous intragenic deletional mutations, involving exons 3 to 4, exon 3, exon 4, and exo 5 in 10 families (17 affected individuals). In addition to the exonic deletions, we identified a novel one‐base deletion involving exon 5 in two families (2 affected individuals). All mutations so far found were deletional types in which large exonic deletion accounted for 50% (17 of 34) and the one‐base deletion accounted for 6% (2/34); in the remaining, no homozygous mutations were found in the coding regions. Our findings indicate that loss of function of the Parkin protein results in the clinical phenotype of AR‐JP and that subregions between introns 2 and 5 of the <jats:italic>Parkin</jats:italic> gene are mutational hot spots.</jats:p>

収録刊行物

被引用文献 (25)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ