Prevalence of carriers of premutation-size alleles of the FMR1 gene-and implications for the population genetics of the fragile X syndrome

Journal Article · Wed Nov 01 04:00:00 EST 1995 · American Journal of Human Genetics

OSTI ID:209891

Rousseau, F; Rouillard, P; Morel, M L ^[1]

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1. Universite Laval, Quebec City (Canada); and others

The fragile X syndrome is the second leading cause of mental retardation after Down syndrome. Fragile X premutations are not associated with any clinical phenotype but are at high risk of expanding to full mutations causing the disease when they are transmitted by a carrier woman. There is no reliable estimate of the prevalence of women who are carriers of fragile X premutations. We have screened 10,624 unselected women by Southern blot for the presence of FMR1 premutation alleles and have confirmed their size by PCR analysis. We found 41 carriers of alleles with 55-101 CGG repeats, a prevalence of 1/259 women (95% confidence interval 1/373-1/198). Thirty percent of these alleles carry an inferred haplotype that corresponds to the most frequent haplotype found in fragile X males and may indeed constitute premutations associated with a significant risk of expansion on transmission by carrier women. We identified another inferred haplotype that is rare in both normal and fragile X chromosomes but that is present on 13 (57%) of 23 chromosomes carrying FMR1 alleles with 53-64 CGG repeats. This suggests either (1) that this haplotype may be stable or (2) that the associated premutation-size alleles have not yet reached equilibrium in this population and that the incidence of fragile X syndrome may increase in the future. 42 refs., 3 figs., 4 tabs.

• OSTI ID: 209891
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 57; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
GENE MUTATIONS
GENES
GENOTYPE
HEREDITARY DISEASES
HUMAN X CHROMOSOME
MENTAL DISORDERS
MUTATION FREQUENCY
NUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
RISK ASSESSMENT
SCREENING
SEX DEPENDENCE
SIZE