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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1996 Dec;59(6):1252–1261.

Familial transmission of the FMR1 CGG repeat.

S L Nolin 1, F A Lewis 3rd 1, L L Ye 1, G E Houck Jr 1, A E Glicksman 1, P Limprasert 1, S Y Li 1, N Zhong 1, A E Ashley 1, E Feingold 1, S L Sherman 1, W T Brown 1
PMCID: PMC1914886  PMID: 8940270

Abstract

To better define the nature of FMR1 CGG-repeat expansions, changes in allele sizes for 191 families with fragile X and for 33 families with gray-zone repeats (40-60) were analyzed. Expansion of the fragile X chromosome to the full mutation was seen in 13.4% of offspring from premutation mothers with 56-59 repeats, 20.6% of those with 60-69 repeats, 57.8% of those with 70-79 repeats, 72.9% of those with 80-89 repeats, and 97.3% of those with 90-199 repeats. For premutation fathers, the majority (62%) of their daughters had a larger repeat number, while a few had either a smaller (22%) or the same (16%) repeat number, compared with their fathers' sizes. However, daughters with a smaller repeat number were observed only if their fathers had > or = 80 repeats. Fifteen (39.5%) of 38 such daughters carried a smaller repeat than did their fathers. We observed that a similar repeat number was inherited more often than expected by chance, among the members of a sibship segregating fragile X. This familial clustering, observed in the offspring of both males and females with a premutation, implies there may be an additional factor, independent of parental repeat size, that influences CGG-repeat instability. Instability in gray-zone allele transmissions was observed in 25% of alleles with 50-60 CGGs but in <8% of those with 40-49 CGGs. Examination of gray-zone allele organization revealed that long tracts of pure CGGs (>34) are not always unstably transmitted. These results raise new questions regarding the familial factors that may determine transmission expansions.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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