Description:
ACHONDROPLASIA; ACH
FIBROBLAST GROWTH FACTOR RECEPTOR 3; FGFR3
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Connective Tissue, Muscle, and Bone |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Molecular characterization after cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227. |
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| 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).
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| Gene |
FGFR3 |
| Chromosomal Location |
4p16.3 |
| Allelic Variant 2 |
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).
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| Remarks |
Mother and father are also affected; small thorax and extremely short limbs noted at birth; large head; large anterior fontanel; short hands with typical severe trident appearance; severe shortening of ribs and long bones; see GM11317 Fibroblast; donor subject is homozygous 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)] |
| Wang CY, Tang YA, Lee IW, Chang FM, Chien CW, Pan HA, Sun HS, Development and validation of an expanded targeted sequencing panel for non-invasive prenatal diagnosis of sporadic skeletal dysplasia BMC medical genomics14:212 2021 |
| PubMed ID: 34789231 |
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| 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 |
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