Mutation Detection in Machado-Joseph Disease Using Repeat Expansion Detection

摘要: Several neurological disorders have recently been explained through the discovery of expanded DNA repeat sequences. Among these is Machado-Joseph disease, one most common spinocerebellar ataxias (MJD/SCA3), caused by a CAG expansion on chromosome 14. A useful way detecting sequence mutations offered detection method (RED), in which thermostable ligase used to detect expansions directly from genomic DNA. We RED families with either MJD/SCA3 or previously uncharacterized ataxia (SCA). Five and SCA family where linkage SCA1–5 had excluded were analyzed polymerase chain reaction (PCR). An represented products 180–270 bp segregated (p < 0.00001) five (n = 60) PCR corresponding 66–80 copies observed all affected individuals. also detected 210-bp product segregating disease 0.01) non-SCA1–5 16), suggesting involvement pathophysiology. analysis subsequently revealed an elongated allele members. correlated at locus. demonstrate added usefulness complicated phenotyping problems gradually developing adult-onset disorders, as examined. The informative without any knowledge flanking This particularly when studying diseases mutated gene unknown. conclude that reliable for analyzing sequences genome.