BACKGROUND: The C749G (Pro250Arg) mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) has been found in patients with various types of craniosynostosis. We aimed to find out the proportion of cases of apparently non-syndromic coronal craniosynostosis attributable to this mutation. METHODS: We studied 26 patients with coronal craniosynostosis but no syndromic diagnosis, who were referred to a supra-regional specialist centre. Genomic DNA was analysed by PCR and restriction-enzyme digestion to identify the C749G mutation in FGFR3. Family members of patients found to have the mutation were also tested. FINDINGS: Eight (31%) of the 26 probands were heterozygous for the C749G mutation. In two cases, the mutation showed autosomal dominant transmission with evidence of variable expressivity; the remaining six cases were sporadic. We demonstrated in six families that the mutation had arisen de novo from clinically unaffected parents. INTERPRETATION: The C749G mutation in FGFR3 is a frequent cause of apparently non-syndromic coronal craniosynostosis. Our finding will aid genetic counselling and prenatal diagnosis. The mutation rate at this nucleotide is one of the highest described in the human genome.
BACKGROUND: The C749G (Pro250Arg) mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) has been found in patients with various types of craniosynostosis. We aimed to find out the proportion of cases of apparently non-syndromic coronal craniosynostosis attributable to this mutation. METHODS: We studied 26 patients with coronal craniosynostosis but no syndromic diagnosis, who were referred to a supra-regional specialist centre. Genomic DNA was analysed by PCR and restriction-enzyme digestion to identify the C749G mutation in FGFR3. Family members of patients found to have the mutation were also tested. FINDINGS: Eight (31%) of the 26 probands were heterozygous for the C749G mutation. In two cases, the mutation showed autosomal dominant transmission with evidence of variable expressivity; the remaining six cases were sporadic. We demonstrated in six families that the mutation had arisen de novo from clinically unaffected parents. INTERPRETATION: The C749G mutation in FGFR3 is a frequent cause of apparently non-syndromic coronal craniosynostosis. Our finding will aid genetic counselling and prenatal diagnosis. The mutation rate at this nucleotide is one of the highest described in the human genome.
Authors: Andrew O M Wilkie; Jo C Byren; Jane A Hurst; Jayaratnam Jayamohan; David Johnson; Samantha J L Knight; Tracy Lester; Peter G Richards; Stephen R F Twigg; Steven A Wall Journal: Pediatrics Date: 2010-07-19 Impact factor: 7.124
Authors: M Oldridge; I K Temple; H G Santos; R J Gibbons; Z Mustafa; K E Chapman; J Loughlin; A O Wilkie Journal: Am J Hum Genet Date: 1999-02 Impact factor: 11.025
Authors: D Johnson; S W Horsley; D M Moloney; M Oldridge; S R Twigg; S Walsh; M Barrow; P R Njølstad; J Kunz; G J Ashworth; S A Wall; L Kearney; A O Wilkie Journal: Am J Hum Genet Date: 1998-11 Impact factor: 11.025
Authors: Sahan V Rannan-Eliya; Indira B Taylor; I Marieke De Heer; Ans M W Van Den Ouweland; Steven A Wall; Andrew O M Wilkie Journal: Hum Genet Date: 2004-07-07 Impact factor: 4.132
Authors: Suzanne L Mansour; Stephen R F Twigg; Rowena M Freeland; Steven A Wall; Chaoying Li; Andrew O M Wilkie Journal: Hum Mol Genet Date: 2008-09-25 Impact factor: 6.150