TY - JOUR
T1 - Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I
AU - Jodice, Carla
AU - Malaspina, Patrizia
AU - Persichetti, Francesca
AU - Novelletto, Andrea
AU - Spadaro, Maria
AU - Giunti, Paola
AU - Morocutti, Cristoforo
AU - Terrenato, Luciano
AU - Harding, Anita E.
AU - Frontali, Marina
PY - 1994
Y1 - 1994
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028229119&partnerID=8YFLogxK
M3 - Article
SN - 0002-9297
VL - 54
SP - 959
EP - 965
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -