Relationship of expansion of CGG repeats and X-inactivation with expression of fra(X) (q27.3) in heterozygotes

Journal Article · Fri Jul 15 04:00:00 EDT 1994 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/ajmg.1320510427· OSTI ID:62052

Mingroni-Netto, R C; Fernandes, J G; Vianna-Morgante, A M ^[1]

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1. Univ. of Sao Paulo (Brazil)

Expression of the fragile site Xq27.3 was investigated in 82 heterozygotes (58 normal and 24 mentally impaired) diagnosed by DNA analysis. EcoRI and EagI DNA digests were probed with StB12.3. This allowed the detection of the expansion of the CGG repeat of the FMR1 gene and the methylation pattern of the adjacent CpG island. Heterozygotes with {Delta} {le} 400 bp (52/82) were all mentally normal and manifested fra(X) in less than 3% of the cells or did not express it. Unmethylated mutant alleles were always observed. About two thirds of females with {Delta} > 500 bp (21/30) showed fra(X) frequencies above 3% (3 normal and 18 mentally impaired). Lower frequencies of fra(X) or negative results were observed in the remaining 9 females (3 normal and 6 affected). The large mutant alleles were always methylated. Therefore, while {Delta} {le} 400 bp is always associated with negative or low expression of fra(X), larger expansions are not present exclusively in heterogeneous with high frequencies of fra(X). In 25 of 30 heterozygotes with {Delta} > 500 bp, active and inactive normal alleles were observed. Three fra(X)-negative or low manifesting heterozygotes showed completely skewed X-inactivation, with the normal allele either active or inactive. Two females with high frequencies of fra(X) always had the normal allele inactivated. Densitometry studies showed no difference in the inactivation of the normal allele between heterozygotes who manifested fra(X) or not. Thus fra(X) expression does not seem to be influenced by X-inactivation. 10 refs., 1 fig., 2 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 62052
• Journal Information: American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 4 Vol. 51; ISSN 0148-7299; ISSN AJMGDA
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
DENSITOMETERS
GENE MUTATIONS
GENES
HEREDITARY DISEASES
HUMAN X CHROMOSOME
HYBRIDIZATION
MENTAL DISORDERS
METHYLATION
PHENOTYPE
SIZE