Premium
Anticipation and intergenerational repeat instability in spinocerebellar ataxia type 17
Author(s) -
Rasmussen Astrid,
De Biase Irene,
FragosoBenítez Marcela,
MacíasFlores Marco Antonio,
Yescas Petra,
Ochoa Adriana,
Ashizawa Tetsuo,
Alonso María Elisa,
Bidichandani Sanjay I.
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21139
Subject(s) - anticipation (artificial intelligence) , spinocerebellar ataxia , trinucleotide repeat expansion , allele , genetics , ataxia , biology , psychology , neuroscience , gene , computer science , artificial intelligence
Spinocerebellar ataxia type 17 (SCA17) is caused by expansion of a CAG/CAA repeat in the TBP gene. Most pathogenic alleles are interrupted and are stably transmitted from parent to offspring without anticipation. We identified three SCA17 families with expansion of uninterrupted alleles, thus greatly increasing the number of known intergenerational transmissions of such alleles. We found that uninterrupted SCA17 alleles are unstable, associated with anticipation, and show a paternal expansion bias that increases with age. Even small increments in repeat length resulted in inordinate increases in anticipation. Anticipation was also associated with childhood presentation. Sequencing of all SCA17 alleles is required for effective genetic counseling. Ann Neurol 2007