An FMR1 premutation of 47 CGG repeats in two brothers from a fragile X family

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

OSTI ID:134184

Carson, N L; Dawson, A J; Chudley, A E ^[1]

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1. Univ. of Manitoba (Canada)

With the cloning of the FMR1 gene, direct mutation analysis is now possible for those families with proven CGG expansion, thus providing a more accurate determination of carrier status than both cytogenetic analysis and linked marker analysis. Individuals from a fragile X positive family previously studied using linked markers were analyzed for CGG repeat size by PCR amplification and Southern blot. Two individuals previously given an 8% risk for being transmitting males were found to have 47 CGG repeats which could be considered normal, and thus be consistent with the linked marker results. However, analysis of one daughter and grandchild has shown that this allele is meiotically unstable, with allele size increasing from 47 to 48 to 49 from father to daughter to grandaughter. In addition, CGG repeat analysis of a sister of these two individuals has indicated that their mother, who is an obligate premutation carrier, must have had a normal allele of 29, thus suggesting the 47 allele represents a premutation in these males. We conclude that FMR1 CGG allele sizes of as small as 47 can be meiotically unstable with presumably an increased risk of expansion to a full mutation in future generations. This example illustrates the importance of analyzing additional family members for the presence of instability in cases where CGG allele sizes in the 40`s are found.

• OSTI ID: 134184
• 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
BIOLOGICAL MARKERS
DNA-CLONING
GENE MUTATIONS
GENES
GENETICS
HEREDITARY DISEASES
HUMAN X CHROMOSOME
INSTABILITY
MEIOSIS
MENTAL DISORDERS
NUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
RISK ASSESSMENT
SIZE