Exclusive paternal origin of new mutations in Apert syndrome.
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.
Moloney
D M
DM
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Slaney
S F
SF
Oldridge
M
M
Wall
S A
SA
Sahlin
P
P
Stenman
G
G
Wilkie
A O
AO
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
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