Expanded IT-15 genes in patients without known family history of Huntington Disease
- North York General Hospital, Toronto (Canada); and others
The NYGH laboratory is funded by the Ontario Ministry of Health to provide DNA-based diagnostic and predictive testing for HD through a network of provincial Genetics centres. To date, samples from 146 apparently independent kindreds were received to test and/or bank for HD. Not all have been assayed for size of the IT-15 gene, but in 19 cases an expansion (> 39 CAG repeats) was found despite lack of known family history. These cases were classified according to the likelihood that they are true {open_quotes}new{close_quotes} full expansions in IT-15. Six were unlikely, due to a lack of information (adoption, history uncertain, or pedigree not provided). Ten cases were considered possible or probable based on a good negative family history with parents who were asymptomatic beyond age 50 but family samples unavailable. For one of those, parents are deceased, but inference of parental alleles from the proband`s sibship suggests a pre-mutation allele of approximately 30 repeats. In 3 cases, a new expansion was considered proven. One was first ascertained by another laboratory and reported elsewhere. For another, the proband`s father has one allele of about 35 repeats. In a third remarkable case, the proband has an expanded allele near 50 repeats and a normal sized allele that matches one maternal allele. The father`s larger allele has 30+/-1 repeats. Paternity was established by concordance of 10 independent polymorphic alleles. Additional family samples may help to assess the allelic stability. This prevalence of new HD cases was unanticipated before discovery of the predisposing gene, but has emerged over the first year of direct diagnostic testing and may foreshadow greater demand for testing as the extended families become aware of their risks. These cases provoke new questions about interpretation of DNA data for patients, raise ethical concerns about informing extended families, and special counselling issues for families to whom HD is a new entity.
- OSTI ID:
- 134176
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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