Mosaicism for an FMR1 gene deletion in a fragile X female.

Journal Article (Journal Article)

Most cases of fragile X syndrome result from expansion of CGG repeats in the FMR1 gene; deletions and point mutations of FMR1 are much less common. Mosaicism for an FMR1 full mutation with a deletion or with a normal allele has been reported in fragile X males. Here we report on a fragile X female who is mosaic for an FMR1 full mutation and an intragenic deletion. The patient is a 4-year-old girl with developmental delay, autistic-like behaviors, and significant speech and language abnormalities. Southern blotting demonstrated the presence of a methylated full mutation, a normal allele in methylated and unmethylated forms, and an additional fragment smaller than the normal methylated allele. This result indicates that the patient is mosaic for a full mutation and a deletion, in the presence of a normal allele. By DNA sequence analysis, we mapped the 5' breakpoint 63/65 bp upstream from the CGG repeat region and the 3' breakpoint 86/88 bp downstream of the CGG repeats within the FMR1 gene. The deletion removed 210 bp, including the entire CGG repeat region. The full mutation was inherited from a premutation in the patient's mother. The deletion, which remained methylated at the Eag I and Nru I sites, was probably derived from the full mutation allele. Mosaicism of this type is rare in females with a fragile X mutation but should be kept in mind in the interpretation of Southern blots.

Full Text

Duke Authors

Cited Authors

  • Fan, H; Booker, JK; McCandless, SE; Shashi, V; Fleming, A; Farber, RA

Published Date

  • July 15, 2005

Published In

Volume / Issue

  • 136 / 2

Start / End Page

  • 214 - 217

PubMed ID

  • 15940701

International Standard Serial Number (ISSN)

  • 1552-4825

Digital Object Identifier (DOI)

  • 10.1002/ajmg.a.30807


  • eng

Conference Location

  • United States