title: The effect of CAT trinucleotide interruptions on the age at onset of spinocerebellar ataxia type 1 (SCA1).
abstract: The effect of CAT trinucleotide interruptions in the CAG trinucleotide repeats of the SCA1 gene on the age at onset of spinocerebellar ataxia type 1 (SCA1) was investigated. The number of CAG repeats in SCA1 was determined by polymerase chain reaction (PCR) analysis, and the presence of CAT interruptions was assessed on the basis of the sensitivity of the PCR products to the restriction endonuclease SfaNI, which recognises CAT trinucleotides. Only one in 17 expanded SCA1 alleles from 17 SCA1 patients was interrupted by CAT. The SfaNI sensitive SCA1 allele from this single patient contained 58 CAG repeats, which would predict an age at onset of SCA1 of 22.0 years, in contrast to the actual 50 years. In addition, the brain stem atrophy of this patient was mild compared with that of a patient with 52 uninterrupted CAG repeats. A sequence analysis showed that the repeat portion of the patient contained (CAG)45CATCAG CAT(CAG)10. From these results, we suggest that the age at onset of SCA1 is not determined by the total number of CAG repeats (58) but by the number of uninterrupted CAG repeats.
authors.affiliation: Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: Z
authors.initials: Z
authors.lastname: Matsuyama
authors.forename: Y
authors.initials: Y
authors.lastname: Izumi
authors.forename: M
authors.initials: M
authors.lastname: Kameyama
authors.forename: H
authors.initials: H
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D016133:Polymerase Chain Reaction; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000473:pathology; D019680:Trinucleotide Repeat Expansion
chemical_list: D015252:Deoxyribonucleases, Type II Site-Specific; C065993:endodeoxyribonuclease SfaNI