Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Feb;72(2):454-64.
doi: 10.1086/367713. Epub 2003 Jan 14.

Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles

Sarah L Nolin  1 , W Ted Brown, Anne Glicksman, George E Houck Jr, Alice D Gargano, Amy Sullivan, Valérie Biancalana, Karen Bröndum-Nielsen, Helle Hjalgrim, Elke Holinski-Feder, Frank Kooy, John Longshore, James Macpherson, Jean-Louis Mandel, Gert Matthijs, Francois Rousseau, Peter Steinbach, Marja-Leena Väisänen, Harriet von Koskull, Stephanie L Sherman
Affiliations

Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles

Sarah L Nolin et al. Am J Hum Genet. 2003 Feb.

Abstract

The CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1) exhibits remarkable instability upon transmission from mothers with premutation alleles. A collaboration of 13 laboratories in eight countries was established to examine four issues concerning FMR1 CGG-repeat instability among females with premutation (approximately 55-200 repeats) and intermediate (approximately 46-60 repeats) alleles. Our central findings were as follows: (1) The smallest premutation alleles that expanded to a full mutation (>200 repeats) in one generation contained 59 repeats; sequence analysis of the 59-repeat alleles from these two females revealed no AGG interruptions within the FMR1 CGG repeat. (2) When we corrected for ascertainment and recalculated the risks of expansion to a full mutation, we found that the risks for premutation alleles with <100 repeats were lower than those previously published. (3) When we examined the possible influence of sex of offspring on transmission of a full mutation-by analysis of 567 prenatal fragile X studies of 448 mothers with premutation and full-mutation alleles-we found no significant differences in the proportion of full-mutation alleles in male or female fetuses. (4) When we examined 136 transmissions of intermediate alleles from 92 mothers with no family history of fragile X, we found that, in contrast to the instability observed in families with fragile X, most (99/136 [72.8%]) transmissions of intermediate alleles were stable. The unstable transmissions (37/136 [27.2%]) in these families included both expansions and contractions in repeat size. The instability increased with the larger intermediate alleles (19% for 49-54 repeats, 30.9% for 55-59, and 80% for 60-65 repeats). These studies should allow improved risk assessments for genetic counseling of women with premutation or intermediate-size alleles.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Analysis of small premutation alleles from females with full-mutation offspring. Lane 1, female with 30 and 62 repeats. Lane 2, female with 29 and 59 repeats. Lane 3, female with 30 and 61 repeats. Lane 4, female with 30 and 59 repeats. Lane 5, female with 31 and 60 repeats. Lane 6, premutation male with 59 repeats. The two unmarked lanes are pBR322 digested with MspI as a size marker. FMR1 repeat-sizes for 28 and 59 CGGs are indicated (left).
Figure 2
Figure 2
Maternal transmission of intermediate alleles. The maternal repeat-sizes are shown on the X-axis, and the number of offspring on the Y-axis. The offspring with stably inherited alleles are shown in black. Each unstable transmission is shown as a white rectangle with the change in repeat number (+ or −) indicated.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

Electronic-Database Information

    1. American Type Culture Collection, http://www.atc.org (for lymphoblastoid cell line [accession number CRL-2704])
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for fragile X syndrome [MIM 309550])

References

    1. Ashley-Koch AE, Robinson H, Glicksman AE, Nolin SL, Schwartz CE, Brown WT, Turner G, Sherman SL (1998) Examination of factors associated with instability of the FMR1 CGG repeat. Am J Hum Genet 63:776–785 - PMC - PubMed
    1. Brown WT, Houck GE, Jeziorowska A, Levinson F, Ding X, Dobkin C, Zhong N, Henderson J, Brooks SS, Jenkins EC (1993) Rapid fragile X carrier screening and prenatal diagnosis using a nonradioactive PCR test. JAMA 270:1569–1575 - PubMed
    1. Brown WT, Houck GE. Ding X, Zhong N, Nolin S, Glicksman A, Dobkin C, Jenkins EC (1996) Reverse mutations in the fragile X syndrome. Am J Med Genet 64:287–292 - PubMed
    1. Crawford DC, Acuna JM, Sherman SL (2001) FMR1 and the fragile X syndrome: human genome epidemiology review. Genet Med 3:359–371 - PMC - PubMed
    1. Crawford DC, Meadows KL, Newman JL, Taft LF, Scott E, Leslie M, Shubec L, Holmgreen P, Yeargin-Allsopp M, Boyle C, Sherman SL (2002) Prevalence of the fragile X syndrome in African-Americans. Am J Med Genet 110:226–233 - PubMed

Publication types

Substances