An FMR1 premutation of 47 CGG repeats in two brothers from a fragile X family
- Univ. of Manitoba (Canada)
With the cloning of the FMR1 gene, direct mutation analysis is now possible for those families with proven CGG expansion, thus providing a more accurate determination of carrier status than both cytogenetic analysis and linked marker analysis. Individuals from a fragile X positive family previously studied using linked markers were analyzed for CGG repeat size by PCR amplification and Southern blot. Two individuals previously given an 8% risk for being transmitting males were found to have 47 CGG repeats which could be considered normal, and thus be consistent with the linked marker results. However, analysis of one daughter and grandchild has shown that this allele is meiotically unstable, with allele size increasing from 47 to 48 to 49 from father to daughter to grandaughter. In addition, CGG repeat analysis of a sister of these two individuals has indicated that their mother, who is an obligate premutation carrier, must have had a normal allele of 29, thus suggesting the 47 allele represents a premutation in these males. We conclude that FMR1 CGG allele sizes of as small as 47 can be meiotically unstable with presumably an increased risk of expansion to a full mutation in future generations. This example illustrates the importance of analyzing additional family members for the presence of instability in cases where CGG allele sizes in the 40`s are found.
- OSTI ID:
- 134184
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0920
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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