title: Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I.
abstract: Trinucleotide repeat expansion has been found in 64 subjects from 19 families: 57 patients with SCA1 and 7 subjects predicted, by haplotype analysis, to carry the mutation. Comparison with a large set of normal chromosomes shows two distinct distributions, with a much wider variation among expanded chromosomes. The sex of transmitting parent plays a major role in the size distribution of expanded alleles, those with > 54 repeats being transmitted by affected fathers exclusively. Our data suggest that alleles with > 54 repeats have a reduced chance of survival; these appear to be replaced in each generation by further expansion of alleles in the low- to medium-expanded repeat range, preferentially in male transmissions. Detailed clinical follow-up of a subset of our patients demonstrates significant relationships between increasing repeat number on expanded chromosomes and earlier age at onset, faster progression of the disease, and earlier age at death.
authors.affiliation: Dipartimento di Biologia, Università Tor Vergata, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Jodice
authors.forename: P
authors.initials: P
authors.lastname: Malaspina
authors.forename: F
authors.initials: F
authors.lastname: Persichetti
authors.forename: A
authors.initials: A
authors.lastname: Novelletto
authors.forename: M
authors.initials: M
authors.lastname: Spadaro
authors.forename: P
authors.initials: P
authors.lastname: Giunti
authors.forename: C
authors.initials: C
authors.lastname: Morocutti
authors.forename: L
authors.initials: L
authors.lastname: Terrenato
authors.forename: A E
authors.initials: AE
authors.lastname: Harding
authors.forename: M
authors.initials: M
authors.lastname: Frontali
mesh_terms: D000328:Adult; D001483:Base Sequence; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010290:Parents; D010641:Phenotype; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012737:Sex Factors; D013132:Spinocerebellar Degenerations / Q000235:genetics*
chemical_list: D009838:Oligodeoxyribonucleotides