Achondroplasia is the most common form of dwarfism, which occurs in about 1 of every 25,000 births (1). An individual with achondroplasia is very short in stature, averaging around 3 feet 8 inches, with very short stumpy limbs. Achondroplasia dwarfs also have a disproportionately large head with a bossing forehead. They have hyperextendibility in most of their joints, except their elbows, which cannot fully extend. Due to extensive fibular growth, the legs of achondroplasia dwarfs are very bowed. The hands of achodroplasia dwarfs are very broad with short metacarpals, referred to as trident hand (2).
The gene responsible for achndroplasia is Fibroblast Growth Factor Receptor 3, or FGFR3, and is located on at 4p16.3 (2). This is a coding gene with a linear mRNA transcript, which is 4,093 base pairs in length. The mutation coding for the achondroplasia allele is a point mutation at the 1,138th base pair of the gene (2). In most cases the guanine molecule is switched with an adenine molecule, which changes the codon to a glycine molecule instead of an argenine molecule at the 380th amino acid of the polypeptide product. The other type of mutation is at the same location, but the guanine molecule is swapped with a cytosine molecule, which also changes the codon to a glycine molecule (2).
The protein product formed from the FGFR3 molecule is 806 amino acids in length and is used as a receptor molecule in fibroblast cells. The function of the normal gene product contains an extracellular region, composed of three immunoglobulin domains, a hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain (2). These allow normal interactions between fibroblasts resulting in normal bone growth. With a glycine in the place of an argenine, the conformation changes, so the protein does not span the membrane as many times, causing different interactions between fibroblasts, ultimately resulting in abnormal bone growth....
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