title: Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.
abstract: Achondroplasia (ACH) is the most common genetic form of dwarfism. This disorder is inherited as an autosomal dominant trait, although the majority of cases are sporadic. A gene for ACH was recently localized to 4p16.3 by linkage analyses. The ACH candidate region includes the gene encoding fibroblast growth factor receptor 3 (FGFR3), which was originally considered as a candidate for the Huntington's disease gene. DNA studies revealed point mutations in the FGFR3 gene in ACH heterozygotes and homozygotes. The mutation on 15 of the 16 ACH-affected chromosomes was the same, a G-->A transition, at nucleotide 1138 of the cDNA. The mutation on the only ACH-affected chromosome 4 without the G-->A transition at nucleotide 1138 had a G-->C transversion at this same position. Both mutations result in the substitution of an arginine residue for a glycine at position 380 of the mature protein, which is in the transmembrane domain of FGFR3.
authors.affiliation: Department of Biological Chemistry, College of Medicine, University of California, Irvine 92717.
authors.forename: R
authors.initials: R
authors.lastname: Shiang
authors.forename: L M
authors.initials: LM
authors.lastname: Thompson
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Zhu
authors.forename: D M
authors.initials: DM
authors.lastname: Church
authors.forename: T J
authors.initials: TJ
authors.lastname: Fielder
authors.forename: M
authors.initials: M
authors.lastname: Bocian
authors.forename: S T
authors.initials: ST
authors.lastname: Winokur
authors.forename: J J
authors.initials: JJ
authors.lastname: Wasmuth
mesh_terms: D000130:Achondroplasia / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D001402:B-Lymphocytes; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics* / Q000502:physiology; D012150:Polymorphism, Restriction Fragment Length; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3