No evidence of genetic heterogeneity in Crouzon craniofacial dysostosis

✍ Scribed by Hong Wi Ma; Elisabeth Lajeunie; Martine Merrer; Nathalie Parseval; Françoise Serville; Jean Weissenbach; Arnold Munnich; Dominique Renier

• Book ID: 104666005
• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 375 KB
• Volume: 96
• Category: Article
• ISSN: 0340-6717
• DOI: 10.1007/bf00210308

✦ Synopsis

Crouzon craniofacial dysostosis (CFD) is an autosomal dominant form of craniosynostosis characterized by an abnormal skull shape, with hypertelorism, prominent eyes and midfacial retrusion. Recently, a gene for CFD has been mapped to chromosome 10q25-q26 and mutations in exon B of the fibroblast growth factor receptor 2 (FGFR2) gene have been identified. Here, we report the mapping of a CFD gene to chromosome 10q by close linkage to probe AFMa197wb1 at locus D10 S1483 in six unrelated families of French ancestry (Zmax = 4.69 at theta = 0) and provide additional evidence of genetic homogeneity of this condition. In addition, we report a novel mutation in exon B of the FGFR2 gene (Cys 342 Trp) in familial CFD and describe recurrent mutations at codon 342 as a particularly frequent event in CFD. Since mutations in the extracellular domain of the FGFR2 gene are observed in a few clinically distinct craniosynostosis syndromes (CFD, Jackson-Weiss, Apert and Pfeiffer), the present study gives support to the variable clinical expression of FGFR2 mutations in humans.