title: Interruptions in the expanded ATTCT repeat of spinocerebellar ataxia type 10: repeat purity as a disease modifier?
abstract: Spinocerebellar ataxia type 10 (SCA10) is one of numerous genetic disorders that result from simple repeat expansions. SCA10 is caused by expansion of an intronic ATTCT pentanucleotide repeat tract. It is clinically characterized by progressive ataxia, seizures, and anticipation, which can vary within and between families. We report two SCA10 families showing distinct frequencies of seizures and correlations of repeat length with age at onset. One family displayed uninterrupted ATTCT expansions, whereas the other showed multiple interruptions of the repeat by nonconsensus repeat units, which differed both in the length and/or sequence of the repeat unit. Disease-causing microsatellite expansions have been assumed to be composed of uninterrupted pure repeats. Our findings for SCA10 challenge this convention and suggest that the purity of the expanded repeat element may be a disease modifier.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Tohru
authors.initials: T
authors.lastname: Matsuura
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Pearson
authors.forename: Parul
authors.initials: P
authors.lastname: Jayakar
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Roa
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
mesh_terms: D017668:Age of Onset; D000067736:Ataxin-10; D001483:Base Sequence; D042622:DNA Repeat Expansion / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology
chemical_list: C503889:ATXN10 protein, human; D000067736:Ataxin-10; D009419:Nerve Tissue Proteins