Analysis of FMR-1 locus in a mentally retarded male patient: Mosaicism or duplication?

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134261

Moore, D K; Evans, J P; Levy-Lahad, E ^[1]

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1. Univ. of Washington, Seattle, WA (United States); and others

Analysis of the CGG repeat region in the FMR-1 allele(s) in a mentally retarded male patient showed two discrete and different sized bands in the premutation range. Southern analysis with EcoRI and EagI revealed bands estimated to represent 54 and 139 repeats of the trinucleotide CGG. Neither band was methylated. No normal sized band was detected. The size of the 54 CGG repeat was confirmed by polyacrylamide gel electrophoresis of the PCR product spanning the CGG repeat region; the 139 repeat was too large for this analysis. Two discrete bands, an unexpected result in a male patient, could represent somatic mosaicism of a single allele. However, in other patients, mosaicism results in a smeared band representing a range of fragment sizes rather than 2 discrete bands. Alternatively, two such bands could indicate that our patient has 2 copies on the FMR-1 allele. A cytogenetic analysis was performed to investigate fragile sites or a duplication. No fragile site was observed in 100 unbanded metaphases examined, ruling out the presence of fragile X in greater than 3% of cells with 0.95 confidence. No evidence of rearrangement of the X chromosome was seen in 50 cells examined, ruling out 6% or greater mosaicism at 0.95 confidence level. A duplication of the FMR-1 allele that is below the resolution of these techniques cannot be ruled out. Physical exam of this patient showed characteristic facies of fragile X syndrome and macroorchidism. The patient had an uncle with mental retardation and similar features and a brother with mental retardation. Clinical symptoms of fragile X are not expected in a patient with an unmethylated FMR-1 allele and an expansion in the premutation range. It is unclear whether the features consistent with fragile X syndrome in this patient are related to the observed molecular occurrences at the FMR-1 allele.

• OSTI ID: 134261
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BANDING TECHNIQUES
CHROMOSOMAL ABERRATIONS
CONGENITAL MALFORMATIONS
DETECTION
ELECTROPHORESIS
GENES
HUMAN X CHROMOSOME
MALES
MENTAL DISORDERS
METHYLATION
MOSAICISM
MUTATIONS
NUCLEOTIDES
POLYMERASE CHAIN REACTION
SIZE
STATISTICS