Description:
HYPOCHONDROPLASIA; HCH
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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Hispanic/Latino
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Relation to Proband
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proband
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Confirmation
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Molecular characterization before 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 |
FGFR3 |
| Chromosomal Location |
4p16.3 |
| Allelic Variant 1 |
134934.0010; HYPOCHONDROPLASIA |
| Identified Mutation |
ASN540LYS, 1620C>A; In 8 out of 14 unrelated patients with hypochondroplasia (146000), Bellus et al. (1995) found a C-to-A transversion at nucleotide 1620 of the FGFR3 gene, resulting in an asn540-to-lys (N540K) substitution in the proximal tyrosine kinase domain of the protein. This mutation was demonstrated in the severely affected woman thought to represent a hypochondroplasia/achondroplasia compound heterozygote (McKusick et al., 1973); the other allele carried the common achondroplasia mutation: gly380-to-arg (134934.0001). Prinos et al. (1995) found the same mutation in 4 cases and confirmed its occurrence in the hypochondroplasia/achondroplasia compound heterozygote.
Bellus et al. (1995) referred to the nucleotide as 1620; Prinos et al. (1995) referred to the nucleotide as 1659. Both groups numbered the amino acid as 540.
Prinster et al. (1998) selected 18 patients with a phenotype compatible with hypochondroplasia based on the most common radiologic criteria. The presence of the N540K mutation was verified by restriction enzyme digestions in 9 of the 18 patients. Although similar in phenotype to patients without the mutation, these 9 had the additional feature of relative macrocephaly. Furthermore, the association of the unchanged or narrow interpedicular distance with the fibula longer than the tibia was more common in patients with the N540K mutation.
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| Remarks |
Rhizomelic short stature; developmental delays; seizure disorder; donor subject has a C>A transversion at nucleotide 1620 in exon 13 of the FGFR3 gene, resulting in an asn540-to-lys [Asn540Lys (N540K)] substitution in the proximal tyrosine kinase domain of the protein |
| Moura S, Hartl I, Brumovska V, Calabrese PP, Yasari A, Striedner Y, Bishara M, Mair T, Ebner T, Schütz GJ, Sevcsik E, Tiemann-Boege I, Exploring FGFR3 Mutations in the Male Germline: Implications for Clonal Germline Expansions and Paternal Age-Related Dysplasias Genome biology and evolution16: 2024 |
| PubMed ID: 38411226 |
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