title: Mitotic stability of fragile X mutations in differentiated cells indicates early post-conceptional trinucleotide repeat expansion.
abstract: We demonstrate here that somatic variation of CGG repeat length is based on a mosaic of cells with different but stable FMR-1 alleles and does not reflect permanent mitotic instability. The length of a particular allele in an individual cell was maintained in progeny cells establishing a clone. The mutation patterns of multiple repeats in the DNA of fetal tissues were identical and did not significantly change during proliferation in vitro. It is proposed that genotype mosaicism and expansion to full mutation are generated post-conceptionally by the same molecular mechanism in a particular window of early development.
authors.affiliation: Abteilung Klinische Genetik, Universität Ulm, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Wöhrle
authors.forename: I
authors.initials: I
authors.lastname: Hennig
authors.forename: W
authors.initials: W
authors.lastname: Vogel
authors.forename: P
authors.initials: P
authors.lastname: Steinbach
mesh_terms: D000483:Alleles; D002454:Cell Differentiation; D002455:Cell Division; D002999:Clone Cells / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008938:Mitosis; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010920:Placenta / Q000473:pathology; D016601:RNA-Binding Proteins; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human