title: Mosaicism for an FMR1 gene deletion in a fragile X female.
abstract: 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.
authors.affiliation: Department of Pathology & Laboratory Medicine, The University of North Carolina at Chapel Hill, 27599, USA.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Fan
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Booker
authors.forename: Shawn E
authors.initials: SE
authors.lastname: McCandless
authors.forename: Vandana
authors.initials: V
authors.lastname: Shashi
authors.forename: Alison
authors.initials: A
authors.lastname: Fleming
authors.forename: Rosann A
authors.initials: RA
authors.lastname: Farber
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D004247:DNA; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human