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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acrocephalosyndactylia / genetics*
-
Adult
-
Base Sequence
-
Cytosine
-
DNA Mutational Analysis
-
DNA Primers
-
Fathers
-
Female
-
Gene Frequency
-
Genetic Variation
-
Genomic Imprinting*
-
Genotype
-
Guanine
-
Haplotypes
-
Humans
-
Male
-
Maternal Age
-
Models, Genetic
-
Molecular Sequence Data
-
Paternal Age
-
Pedigree
-
Point Mutation
-
Polymerase Chain Reaction
-
Polymorphism, Genetic
-
Receptor Protein-Tyrosine Kinases / genetics*
-
Receptor, Fibroblast Growth Factor, Type 2
-
Receptors, Fibroblast Growth Factor / genetics*
-
Restriction Mapping
Substances
-
DNA Primers
-
Receptors, Fibroblast Growth Factor
-
Guanine
-
Cytosine
-
FGFR2 protein, human
-
Receptor Protein-Tyrosine Kinases
-
Receptor, Fibroblast Growth Factor, Type 2