Expansion of an FMR1 grey-zone allele to a full mutation in two generations

Isabel Fernandez-Carvajal, Blanca Lopez Posadas, Ruiqin Pan, Christopher Raske, Paul J Hagerman, Flora Tassone

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Fragile X Syndrome is caused by the expansion of an unstable CGG-repeat tract in the 5′-UTR of the FMR1 gene, which generally results in transcriptional silencing and consequent absence of the FMR1 protein. To date, the smallest premutation allele reported to expand to a full mutation allele in a single generation is 59 CGG repeats. Here, we report a single-generation expansion to a full mutation allele (male with ∼538 CCG repeats) from a mother who is a carrier of a premutation allele of 56 CGG repeats. Furthermore, the maternal grandfather was a carrier of a gray (or intermediate)-zone allele (45 to 54 repeats) of 52 CGG repeats. Thus, in this family, a gray-zone allele expanded to the full mutation range in two generations. Interestingly, the two AGG interruptions present in the grandfather's allele were absent in the mother's premutation allele. These observations underscore the need to consider carriers of alleles of greater than 55 CGG repeats as being at risk for transmission of a full mutation allele in a single generation, and those with even smaller alleles in the gray zone as being at risk of having grandchildren with full mutation alleles.

Original languageEnglish (US)
Pages (from-to)306-310
Number of pages5
JournalJournal of Molecular Diagnostics
Volume11
Issue number4
DOIs
StatePublished - Jul 2009

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Alleles
Mutation
Mothers
Fragile X Syndrome
5' Untranslated Regions
Genes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine

Cite this

Expansion of an FMR1 grey-zone allele to a full mutation in two generations. / Fernandez-Carvajal, Isabel; Posadas, Blanca Lopez; Pan, Ruiqin; Raske, Christopher; Hagerman, Paul J; Tassone, Flora.

In: Journal of Molecular Diagnostics, Vol. 11, No. 4, 07.2009, p. 306-310.

Research output: Contribution to journalArticle

Fernandez-Carvajal, Isabel ; Posadas, Blanca Lopez ; Pan, Ruiqin ; Raske, Christopher ; Hagerman, Paul J ; Tassone, Flora. / Expansion of an FMR1 grey-zone allele to a full mutation in two generations. In: Journal of Molecular Diagnostics. 2009 ; Vol. 11, No. 4. pp. 306-310.
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