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Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). This frequently occurs as a new mutation, manifesting one of the highest documented rates for any transversion in the human genome. To understand the biology of this mutation, we have investigated its parental origin, and the ages of the parents, in 19 families with de novo c.749C>G mutations. All ten informative cases originated from the paternal allele (95% confidence interval 74-100% paternal); the average paternal age at birth overall was 34.7 years. An exclusive paternal origin of mutations, and increased paternal age, were previously described for a different mutation (c.1138G>A) of the FGFR3 gene causing achondroplasia, as well as for mutations of the related FGFR2 gene causing Apert, Crouzon and Pfeiffer syndromes. We conclude that similar biological processes are likely to shape the occurrence of this c.749C>G mutation as for other mutations of FGFR3 as well as FGFR2.

Original publication

DOI

10.1007/s00439-004-1151-5

Type

Journal article

Journal

Hum Genet

Publication Date

08/2004

Volume

115

Pages

200 - 207

Keywords

Adult, Age Factors, Amino Acid Substitution, Child, Craniosynostoses, DNA Mutational Analysis, Female, Humans, Male, Mutation, Missense, Paternal Age, Pedigree, Polymerase Chain Reaction, Protein-Tyrosine Kinases, Receptor, Fibroblast Growth Factor, Type 3, Receptors, Fibroblast Growth Factor, Risk Factors, Syndrome