Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I.
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.
Jodice
C
C
Dipartimento di Biologia, Università Tor Vergata, Rome, Italy.
Malaspina
P
P
Persichetti
F
F
Novelletto
A
A
Spadaro
M
M
Giunti
P
P
Morocutti
C
C
Terrenato
L
L
Harding
A E
AE
Frontali
M
M
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*
D009838:Oligodeoxyribonucleotides