title: Expansion of an FMR1 grey-zone allele to a full mutation in two generations.
abstract: Fragile X Syndrome is caused by the expansion of an unstable CGG-repeat tract in the 5'-UTR of the FMR1 gene, which generally results in transcriptional silencing and consequent absence of the FMR1 protein. To date, the smallest premutation allele reported to expand to a full mutation allele in a single generation is 59 CGG repeats. Here, we report a single-generation expansion to a full mutation allele (male with approximately 538 CCG repeats) from a mother who is a carrier of a premutation allele of 56 CGG repeats. Furthermore, the maternal grandfather was a carrier of a gray (or intermediate)-zone allele (45 to 54 repeats) of 52 CGG repeats. Thus, in this family, a gray-zone allele expanded to the full mutation range in two generations. Interestingly, the two AGG interruptions present in the grandfather's allele were absent in the mother's premutation allele. These observations underscore the need to consider carriers of alleles of greater than 55 CGG repeats as being at risk for transmission of a full mutation allele in a single generation, and those with even smaller alleles in the gray zone as being at risk of having grandchildren with full mutation alleles.
authors.affiliation: Laboratorio de Genética Humana, Unidad de Diagnóstico Genético y Perinatal, Instituto de Biología y Genética Molecular, Universidad de Valladolid-CSIC, Valladolid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fernandez-Carvajal
authors.forename: Blanca
authors.initials: B
authors.lastname: Lopez Posadas
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Pan
authors.forename: Christopher
authors.initials: C
authors.lastname: Raske
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1