NA08855
DNA from Fibroblast
Description:
THANATOPHORIC DYSPLASIA; TD
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 |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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White
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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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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| Passage Frozen |
4 |
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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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| MUTATION VERIFICATION |
The gene mutation in this cell line was confirmed by sequencing and FRET probe analysis. |
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| Gene |
FGFR3 |
| Chromosomal Location |
4p16.3 |
| Allelic Variant 1 |
134934.0005; THANATOPHORIC DYSPLASIA, TYPE I; TD1 |
| Identified Mutation |
ARG248CYS; Of 39 individuals with type I thanatophoric dysplasia (187600), Tavormina et al. (1995) found an arg248-to-cys mutation in 22 and a ser371-to-cys mutation (134934.0006) in 1. Both of these mutations were in the extracellular region of the protein. Amino acid substitution resulted from a C-to-T transition at nucleotide 742.
Although type II thanatophoric dysplasia cases have been found to have a single recurrent K650E change (134934.0004), type I cases have different mutations affecting either the extracellular or intracellular domains of FGFR3. However, mutations in the FGFR3 gene were identified in only approximately 60% of the type I TD cases. These findings, and the range of symptoms observed, suggested that type I TD is heterogeneous in genetic background. Pokharel et al. (1996) described a Japanese type I TD patient followed for more than 9 years. They found that the patient had the arg248-to-cys mutation as did 4 other Japanese cases of type I TD. No association was found with the ser371-to-cys mutation.
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| Remarks |
Macrocephaly; macrocranium without evidence of craniosynostosis; severe shortening of the extremities; upper/lower segment ratio is 28/11; radiographs typical of thanatophoric dysplasia; expired on 1st day of life; donor subject has a C>T transition at nucleotide 742 in exon 6 of the FGFR3 gene (742C>T) resulting in a substitution of cysteine for arginine at codon 248 [Arg248Cys (R248C)] |
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