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What genes cause the disease achondroplasia?
Achondroplasia is caused by a mutation in the FGFR3 gene. The official name for this gene is fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) and the official symbol is FGFR3.
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On which chromosome are the genes located?
The FGFR3 gene is located at 4pl6.3. This is the short arm (p) of the fourth chromosome at band position 16.3.
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What are the normal functions of the gene product?
The function of the FGFR3 gene is to code for a receptor protein that is embedded in the cell membrane. When a growth factor interacts with the receptor protein, it triggers a chemical reaction that instructs a bone cell to get ready to grow or divide. The receptor protein regulates bone growth by limiting the formation of bone from cartilage, particularly in the long bones.
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What mutations have been found in these genes?
A mutation in a single base pair of the FGFR3 gene causes achondroplasia. 99% of the time this causes a substitution of the amino acid arginine for glycine at position 380. 28 distinct mutations have been recorded in the literature for this gene, with the achondroplasia mutation being the most frequently mutated site in the human genome. The other mutations cause other diseases (see question 8)
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What are the functions of the mutated gene product?
Mutations in the gene cause the receptor to be overly active, leading to disturbances in bone growth. Different mutations lead to different rates and kinds of bone growth disturbances.
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What laboratories are performing DNA tests for the achondroplasia mutations?
There are 14 laboratories around the world that test for the achondroplasia mutations and other mutations in the FGFR3 gene.
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Are there gene therapies or clinical trials for achondroplasia?
There are currently no clinical trials for achondroplasia, but there are clinical trials for the cancers (see question 8) caused by the FGFR3 gene mutations.
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Do the genes cause any other diseases in addition to achondroplasia?
Mutations in the gene cause seven distinct inherited syndromes: achondroplasia, thanatophoric dwarfism (type 1 and type 2), Crouzon syndrome with acanthosis nigricans, hypochondroplasia, Muenke syndrome, and SADDAN dysplasia. Furthermore, if the FGFR3 gene is mutated in a somatic cell during the adult life of a person, the person will likely develop one of four different cancers, depending in which tissue the mutation arises: bladder cancer, cervical cancer, colorectal cancer, and multiple myeloma. The somatic mutations are often at the same "hot spots" for mutation that cause skeletal dysplasias when they occur in the germ line. Mutations in other genes can also cause these same cancers.
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What names are used to refer to the genes, the gene products and the diseases in these resources?
The official name for this gene is fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) and the official symbol is FGFR3. In addition to the official names, sixteen alternate names and symbols are used for the gene and gene products (FGFR-3, FGFR3_HUMAN, ACH, CEK2, JTK4, HSFGFR3EX, HBGFR, fibroblast growth factor receptor 3, FGFR-3 gene product, FGFR-3 protein, fibroblast growth factor receptor 3 [precursor], tyrosyl protein kinase, protein-tyrosine kinase, human tyrosine kinase JTK4, tyrosine kinase JTK4, and hydroxyarl-protein kinase). The gene has two different gene products (isoforms) called fibroblast growth factor receptor 3, isoform 1 precursor and fibroblast growth factor receptor 3, isoform 2 precursor, although the differences in their function is not understood. The disease achondroplasia is also referred to as achondroplasia syndrome, achondroplasia dwarfism, chondrodystrophia, chondrodystrophia fetalis, chondrodystrophia foetalis, chondrodystrophy syndrome, congential osteosclerosis, and osteosclerosis congenital.
