Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I
- Universita Tor Vergata, Rome (Italy)
- Universita La Sapienza, Rome (Italy)
- Universita La Sapienza, Rome (Italy) Institute of Neurology, London (United Kingdom)
- Institute of Neurology, London (United Kingdom)
- Istituto di Medicina Sperimentale, Rome (Italy)
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. The 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 transmission. Detailed clinical follow-up of a subset of 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.
- OSTI ID:
- 7076096
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 54:6; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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