An Introduction to Achondroplasia Genetics
There are two possible causes of
achondroplasia; genetics plays a role in both. One possible cause is a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene located on chromosome 4. The other possibility is that the gene can be inherited from a parent with achondroplasia.
Achondroplasia Genetics and Mutation
Most people with achondroplasia genetics have average-size parents, which means that the
cause of achondroplasia is a new mutation in the FGFR3 gene. Scientists do not know why this mutation occurs.
Inherited Achondroplasia Genetics
Achondroplasia genetics can also be inherited in an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, one of the parents with achondroplasia passes on the FGFR3 gene to the child.
If one parent has achondroplasia, children have a 50 percent chance of inheriting the FGFR3 gene. If both parents have achondroplasia, children have a one in four chance of inheriting the gene from both parents. Newborns who inherit both genes are considered to have a severe form of achondroplasia, where survival is usually less than 12 months after birth.
Achondroplasia Genetics and the FGFR3 Gene
Although achondroplasia can be inherited, 80 percent of all cases are the result of a sporadic mutation involving the gene encoding FGFR3, situated on chromosome 4.
The protein made by the FGFR3 gene is a receptor that regulates bone growth by limiting the formation of bone from cartilage (a process called ossification), particularly in the long bones. Researchers believe that mutations in the FGFR3 gene cause the receptor to be overly active, which interferes with ossification and leads to the disturbances in bone growth seen with this disorder.
This theory is supported by the knockout mouse model in which the receptor is absent, and so the negative regulation of bone formation is lost. The result is a mouse with excessively long bones and elongated vertebrae, resulting in a long tail. Achondroplastic mouse models are useful tools in developing potential treatments.
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