How to cite this article: Nolin SL, Ding X-h, Houck GE, Brown WT, Dobkin C. 2007. Fragile X full mutation alleles composed of few alleles: Implications for CGG repeat expansion. Am J Med Genet Part A 146A:60–65.
Fragile X full mutation alleles composed of few alleles: Implications for CGG repeat expansion†
Version of Record online: 11 DEC 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 146A, Issue 1, pages 60–65, 1 January 2008
How to Cite
Nolin, S. L., Ding, X.-h., Houck, G. E., Brown, W. T. and Dobkin, C. (2008), Fragile X full mutation alleles composed of few alleles: Implications for CGG repeat expansion. Am. J. Med. Genet., 146A: 60–65. doi: 10.1002/ajmg.a.32087
- Issue online: 19 DEC 2007
- Version of Record online: 11 DEC 2007
- Manuscript Accepted: 23 AUG 2007
- Manuscript Received: 11 APR 2007
- New York State Office of Mental Retardation and Developmental Disabilities
- fragile X;
- trinucleotide repeat disorder
Southern analysis of the FMR1 repeat region has suggested that individuals with the full mutation usually carry a heterogeneous array of FMR1 alleles in somatic tissue that can range from 200 to more than 1,000 repeats. Our studies indicate that this heterogeneity is an artifact generated by ethidium bromide commonly used in Southern analysis. When analyzed in the absence of ethidium bromide, nearly all full mutation individuals carried only one to four major alleles and did not exhibit the heterogeneity often referred to as a “smear” in the literature. Full mutations in chorionic villi, however, exhibited much greater heterogeneity. Nine transmissions from mothers with full mutation alleles to offspring indicated that the full mutations continued to expand in transmission to the next generation. In contrast, analysis of leukocyte DNA from three full mutation males revealed no change in somatic full mutation alleles over many years. Our studies support the hypothesis that the FMR1 CGG repeat instability is limited to very early embryogenesis in the soma. These studies also have clinical importance because the omission of ethidium bromide will facilitate the diagnosis of females with full mutation alleles. © 2007 Wiley-Liss, Inc.