title: Mutations of the fibroblast growth factor receptor-3 gene in achondroplasia.
abstract: Achondroplasia (ACH), the most common cause of chondrodysplasia in man (1 in 15,000 live births), is an autosomal dominant condition of unknown origin characterized by short-limbed dwarfism and macrocephaly. Recently, a gene for ACH has been mapped to chromosome 4p16.3. The genetic interval encompassing the disease gene contains a member of the fibroblast growth factor receptor (FGFR) family which is expressed in articular chondrocytes (FGFR3). We report here recurrent missense mutations, in a CpG doublet of the transmembrane domain of the FGFR3 protein (G380R) in 17 sporadic cases and 6 unrelated familial forms of ACH and show that the mutant genotype segregates with the disease in these families. Thus, it appears that recurrent mutations of a single amino acid in the transmembrane domain of the FGFR3 protein account for all cases (23/23) of achondroplasia in our series.
authors: Service de Génétique, INSERM U 393, Hopital des Enfants, Malades, Paris, France.
authors: F
authors: F
authors: Rousseau
authors: J
authors: J
authors: Bonaventure
authors: L
authors: L
authors: Legeai-Mallet
authors: A
authors: A
authors: Pelet
authors: J M
authors: JM
authors: Rozet
authors: P
authors: P
authors: Maroteaux
authors: M
authors: M
authors: Le Merrer
authors: A
authors: A
authors: Munnich
mesh_terms: D000130:Achondroplasia / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D002645:Chickens; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D005346:Fibroblast Growth Factors; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496365:FGFR3 protein, human; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3