Reversion to Normal of FMR1 Expanded Alleles: A Rare Event in Two Independent Fragile X Syndrome Families

Elisabetta Tabolacci, Maurizio Genuardi, Pietro Chiurazzi, Giulia Maneri, Veronica Nobile, Giovanni Neri, Roberta Pietrobono, Laura Remondini, Matteo Della Monica, Maria Grazia Pomponi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Fragile X syndrome (FXS) is mostly due to the expansion and subsequent methylation of a polymorphic CGG repeat in the 5' UTR of the FMR1 gene. Full mutation alleles (FM) have more than 200 repeats and result in FMR1 gene silencing and FXS. FMs arise from maternal premutations (PM) that have 56-200 CGGs; contractions of a maternal PM or FM are rare. Here, we describe two unaffected boys in two independent FXS families who inherited a non-mosaic allele in the normal and intermediate range, respectively, from their mothers who are carriers of an expanded CGG allele. The first boy inherited a 51 CGG allele (without AGG interruptions) from his mother, who carries a PM allele with 72 CGGs. The other boy inherited from his FM mother an unusual allele with 19 CGGs resulting from a deletion, removing 85 bp upstream of the CGG repeat. Given that transcription of the deleted allele was found to be preserved, we assume that the binding sites for FMR1 transcription factors are excluded from the deletion. Such unusual cases resulting in non-mosaic reduction of maternal CGG expansions may help to clarify the molecular mechanisms underlying the instability of the FMR1 gene.
Lingua originaleEnglish
pagine (da-a)248-260
Numero di pagine13
RivistaGenes
Volume11
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • CGG instability
  • CGG reversion
  • FMR1 gene
  • fragile X syndrome
  • genetic test

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