title: Exclusive paternal origin of new mutations in Apert syndrome.
abstract: Apert syndrome results from one or other of two specific nucleotide substitutions, both C-->G transversions, in the fibroblast growth factor receptor 2 (FGFR2) gene. The frequency of new mutations, estimated as 1 per 65,000 live births, implies germline transversion rates at these two positions are currently the highest known in the human genome. Using a novel application of the amplification refractory mutation system (ARMS), we have determined the parental origin of the new mutation in 57 Apert families: in every case, the mutation arose from the father. This identifies the biological basis of the paternal age effect for new mutations previously suggested for this disorder.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Moloney
authors.forename: S F
authors.initials: SF
authors.lastname: Slaney
authors.forename: M
authors.initials: M
authors.lastname: Oldridge
authors.forename: S A
authors.initials: SA
authors.lastname: Wall
authors.forename: P
authors.initials: P
authors.lastname: Sahlin
authors.forename: G
authors.initials: G
authors.lastname: Stenman
authors.forename: A O
authors.initials: AO
authors.lastname: Wilkie
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D003596:Cytosine; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005220:Fathers; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D018392:Genomic Imprinting; D005838:Genotype; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D008297:Male; D008423:Maternal Age; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010331:Paternal Age; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D017931:DNA Primers; D017468:Receptors, Fibroblast Growth Factor; D006147:Guanine; D003596:Cytosine; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2