MKKS

The MKKS gene provides instructions for making a protein that plays an important role in the formation of the limbs, heart, and reproductive system. The structure of this protein suggests that it may act as a chaperonin, which is a protein that helps fold other proteins. Proteins must be folded into the correct 3-dimensional shape to perform their usual functions in the body. Abnormally folded proteins can also interfere with the functions of normal proteins.

Although the structure of the MKKS protein is similar to that of a chaperonin, some studies have suggested that protein folding may not be this protein's primary function. Within cells, the MKKS protein is associated with structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules, which are proteins that transport materials in cells and help the cell maintain its shape. Researchers speculate that the MKKS protein may be involved in transporting other proteins within the cell.

McKusick-Kaufman syndrome - caused by mutations in the MKKS gene

Two mutations in the MKKS gene have been identified in people with McKusick-Kaufman syndrome in the Old Order Amish population. Each of these mutations changes a single protein building block (amino acid) in the MKKS protein. One mutation replaces the amino acid histidine with the amino acid tyrosine at protein position 84 (written as His84Tyr or H84Y). The other mutation replaces the amino acid alanine with the amino acid serine at protein position 242 (written as Ala242Ser or A242S). Affected Amish people have these two mutations in both copies of the MKKS gene.

The mutations that underlie McKusick-Kaufman syndrome alter the structure of the MKKS protein. Although the altered protein disrupts the development of several parts of the body before birth, it is unclear how MKKS mutations lead to the specific features of this disorder.

other disorders - caused by mutations in the MKKS gene

Mutations in the MKKS gene also cause some cases of a condition called Bardet-Biedl syndrome. The major features of this disorder include vision loss, obesity, extra fingers and toes (polydactyly), learning difficulties, genital abnormalities, and kidney (renal) disease.

More than 20 MKKS mutations have been found to cause Bardet-Biedl syndrome. Some of these mutations change single amino acids in the MKKS protein, while others lead to the production of an abnormally short, nonfunctional version of the protein. Researchers are working to determine how the defective MKKS protein leads to the characteristic features of Bardet-Biedl syndrome.

The signs and symptoms of Bardet-Biedl syndrome overlap significantly with those of McKusick-Kaufman syndrome, which can make the two conditions difficult to tell apart in infancy and early childhood. Although both syndromes can be caused by changes in the MKKS gene, it remains unclear why some mutations cause Bardet-Biedl syndrome and others cause McKusick-Kaufman syndrome.