TY - JOUR
T1 - Interruptions in the expanded ATTCT repeat of spinocerebellar ataxia type 10
T2 - Repeat purity as a disease modifier?
AU - Matsuura, Tohru
AU - Fang, Ping
AU - Pearson, Christopher E.
AU - Jayakar, Parul
AU - Ashizawa, Tetsuo
AU - Roa, Benjamin B.
AU - Nelson, David L.
N1 - Funding Information:
This work was supported by National Ataxia Foundation and National Organization for Rare Disorders grants (to T.M.); National Institutes of Health (NIH) National Institute of Child Health and Human Development grants HD38038 and HD29256 (to D.L.N.); NIH National Institute of Neurological Disorders and Stroke grant NS41547 (to T.A.); by the FRAXA Research Foundation and the BCM Mental Retardation Research Center (to D.L.N.); and by the Canadian Institutes of Health Research (CHIR) and the Fragile X Research Foundation of Canada (to C.E.P). C.E.P. is a CHIR scholar and a Canadian Genetic Disease Network scholar.
PY - 2006/1
Y1 - 2006/1
N2 - 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.
AB - 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.
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U2 - 10.1086/498654
DO - 10.1086/498654
M3 - Article
C2 - 16385455
AN - SCOPUS:29244440698
SN - 0002-9297
VL - 78
SP - 125
EP - 129
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -