title: Mosaicism for FMR1 gene full mutation and intermediate allele in a female foetus: a postzygotic retraction event.
abstract: Fragile X syndrome is caused by the expansion of an unstable CGG repeat in the 5'UTR of FMR1 gene. The occurrence of mosaicism is not uncommon, especially in male patients, whereas in females it is not so often reported. Here we report a female foetus that was subject to prenatal diagnosis, because of her mother being a premutation carrier. The foetus was identified as being a mosaic for an intermediate allele and a full mutation of FMR1 gene, in the presence of a normal allele. The mosaic status was confirmed in three different tissues of the foetus--amniotic fluid, skin biopsy and blood--the last two obtained after pregnancy termination. Karyotype analysis and X-chromosome STR markers analysis do not support the mosaicism as inheritance of both maternal alleles. Oligonucleotide array-CGH excluded an imbalance that could contain the primer binding site with a different repeat size. The obtained results give compelling evidence for a postzygotic expansion mechanism where the foetus mosaic pattern originated from expansion of the mother's premutation into a full mutation and consequent regression to an intermediate allele in a proportion of cells. These events occurred in early embryogenesis before the commitment of cells into the different tissues, as the three tested tissues of the foetus have the same mosaic pattern. The couple has a son with Fragile X mental retardation syndrome and choose to terminate this pregnancy after genetic counselling.
authors.affiliation: Laboratório de Citogenética e Genómica, Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
authors.forename: Susana Isabel
authors.initials: SI
authors.lastname: Ferreira
authors.forename: Luís Miguel
authors.initials: LM
authors.lastname: Pires
authors.forename: José
authors.initials: J
authors.lastname: Ferrão
authors.forename: Joaquim
authors.initials: J
authors.lastname: Sá
authors.forename: Armando
authors.initials: A
authors.lastname: Serra
authors.forename: Isabel Marques
authors.initials: IM
authors.lastname: Carreira
mesh_terms: D000025:Abortion, Eugenic; D000483:Alleles; D000649:Amniocentesis; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009030:Mosaicism; D010375:Pedigree; D011247:Pregnancy
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: 5′ unstranslated region; 5′UTR; Array-CGH; FMR1; FMR1 gene; FMRP; Female mosaicism; Fragile X; Fragile X Mental Retardation 1 gene; Fragile X Mental Retardation Protein; IQ; Intelligence Quotient; PCR; Polymerase Chain Reaction; Postzygotic regression; STR; Short Tandem Repeat; TP PCR; Triplet Repeat Primed PCR; array-Comparative Genomic Hybridization