Achondroplasia
Achondroplasia is a Greek word meaning "without cartilage formation" and is
one of the most common causes of dwarfism. The appearance is of short stature with
disproportionately short arms and legs and a large head. The characteristic facial
features include a prominent forehead and a flattened bridge of the nose.
Although this condition can be inherited in an autosomal dominant manner, 80% of cases are
due to new, sporadic mutations. Mutations involve the gene encoding fibroblast growth
factor receptor 3 (FGFR3), situated on chromosome 4. Most commonly, a point mutation
causes the substitution of arginine for glycine (G380R) in the transmembrane region of the
receptor.
There is growing evidence that mutations of FGF3R confer a "gain of function".
It is proposed that the normal function of FGFR3 is to slow down the formation of bone by
inhibiting the proliferation of chondrocytes, the cells that produce cartilage. The
mutation increases the activity of FGFR3, severely limiting bone growth.
This theory is supported by the knock-out 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 |
