title: Anticipation and intergenerational repeat instability in spinocerebellar ataxia type 17.
abstract: 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.
authors.affiliation: Department of Neurogenetics and Molecular Biology, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico.
authors.forename: Astrid
authors.initials: A
authors.lastname: Rasmussen
authors.forename: Irene
authors.initials: I
authors.lastname: De Biase
authors.forename: Marcela
authors.initials: M
authors.lastname: Fragoso-Benítez
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Macías-Flores
authors.forename: Petra
authors.initials: P
authors.lastname: Yescas
authors.forename: Adriana
authors.initials: A
authors.lastname: Ochoa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.forename: María Elisa
authors.initials: ME
authors.lastname: Alonso
authors.forename: Sanjay I
authors.initials: SI
authors.lastname: Bidichandani
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D020132:Anticipation, Genetic; D002648:Child; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010375:Pedigree; D017678:Sex Distribution; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics*; D035181:TATA-Box Binding Protein / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D035181:TATA-Box Binding Protein