MATN3

Multiple epiphyseal dysplasia

At least 14 different mutations in the MATN3 gene have been shown to cause a mild form of multiple epiphyseal dysplasia. All of the mutations change one protein building block (amino acid) within or close to a region of matrilin-3 called the A-domain. One genetic change accounts for approximately 40 percent of all MATN3 mutations. This mutation replaces the amino acid arginine with the amino acid tryptophan at position 121 (written as Arg121Trp or R121W).

Researchers believe that mutations in the MATN3 gene prevent matrilin-3 from folding properly. Instead of being transported to the extracellular matrix of the chondrocytes, matrilin-3 remains in the endoplasmic reticulum. The endoplasmic reticulum is a structure inside the cell that is involved in protein processing and transport. This cell structure eventually becomes so large that it is no longer able to function normally, and the chondrocyte dies. The premature death of chondrocytes results in diminished growth of the long bones and short stature.