title: G370C mutation in the FGFR3 gene in a Japanese patient with thanatophoric dysplasia.
abstract: Thanatophoric dysplasia (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, relative macrocephaly, platyspondyly and reduced thoracic cavity. It has recently been reported that TD is caused by mutations in the FGFR3 gene. In the present study, we report a missense mutation in the FGFR3 gene in a Japanese patient with TD. The patient was noticed to have typical features of TD type 1 (TD1) at birth. The genomic DNAs of the patient and his parents were isolated from whole blood. DNA fragments of the FGFR3 gene were amplified by polymerase chain reaction, and directly sequenced. The patient was revealed to be heterozygous for a missense mutation G370C, changing codon 370 (GGC) encoding Gly to TGC encoding Cys, but his parents did not have the G370C mutation. The G370C mutation introduces an unpaired cysteine residue in the extracellular domain of FGFR3, which may result in formation of an intermolecular disulfide bond between two mutant FGFR3 monomers and their constitutive activation. In conclusion, we have identified the G370C mutation in the FGFR3 gene in a Japanese TD1 patient.
authors.affiliation: Department of Endocrinology and Metabolism, National Children's Medical Research Center, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Katsumata
authors.forename: T
authors.initials: T
authors.lastname: Kuno
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
authors.forename: S
authors.initials: S
authors.lastname: Mikami
authors.forename: A
authors.initials: A
authors.lastname: Nagashima-Miyokawa
authors.forename: A
authors.initials: A
authors.lastname: Nimura
authors.forename: R
authors.initials: R
authors.lastname: Horikawa
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000483:Alleles; D005346:Fibroblast Growth Factors / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013796:Thanatophoric Dysplasia / Q000235:genetics*
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3