GM08857

GM08857 Fibroblast

Description:

ACHONDROPLASIA; ACH
FIBROBLAST GROWTH FACTOR RECEPTOR 3; FGFR3

Affected:

Yes

Sex:

Male

Age:

34 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Family Member

Relation to Proband

father

Confirmation

Molecular characterization after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected father of GM08859; donor subject is heterozygous for a G>A transition at nucleotide 1138 of the FGFR3 gene resulting in the substitution of arginine for glycine at codon 380 [Gly380Arg (G380R)]

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227.

Gene

FGFR3

Chromosomal Location

4p16.3

Allelic Variant 1

134934.0001; ACHONDROPLASIA; ACH

Identified Mutation

GLY380ARG, 1138G>A; In achondroplasia, codon 380 in the FGFR3 gene is changed from GGG to AGG or CGG (Shiang et al., 1994). Codon 379 is TAC (tyr). Rousseau et al. (1994) found the gly380-to-arg mutation in all 23 cases of achondroplasia studied (17 sporadic and 6 familial). Twenty-two of the 23 probands had the G-to-A transition; only 1 had the G-to-C transversion (134934.0002). See also Ikegawa et al. (1995). Nucleotide 1138 of the FGFR3 gene may be one of the most mutable bases in the human genome. Wilkie (1997) commented that it seems unlikely to be coincidental that the 3 highest germline point mutation rates described in the human (elevated approximately 1000-fold over background) all concern FGFRs: G380R in FGFR3, P250R also in FGFR3 (134934.0014), and S252W in FGFR2 (176943.0010). These 3 mutations result in achondroplasia, Muenke nonsyndromic coronal craniosynostosis, and Apert syndrome, respectively. Increased paternal age associated with achondroplasia and Apert syndrome has long been known, and an exclusively paternal origin of mutation was shown in studies of 57 Apert syndrome patients by Moloney et al. (1996) and in 10 achondroplasia patients by Szabo et al. (1996).

Phenotypic Data

Remarks

Publications

Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ, Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell78:335-42 1994

PubMed ID: 7913883