Ullrich congenital muscular dystrophy (UCMD) is a rare genetic disorder characterized by severe muscle weakness that appears at or soon after birth. Patients also may have muscle spasms and develop problems with their joints, in addition to other symptoms.

UCMD is one of a group of disorders called collagen type 6-related myopathies because they all are caused by mutations in components of collagen type 6.

What is collagen type 6?

Collagen type 6 is a big protein complex that is synthesized using instructions from six different genes: COL6A1COL6A2COL6A3, COL6A4, COL6A5, and COL6A6. COL6A4 was separated into two pieces — COL6A4P1 and COL6A4P2 — by an ancient evolutionary gene rearrangement. COL6A4P1 encodes for a portion of the collagen type 6 complex, while COL6A4P2 is considered a “pseudogene,” which does not encode for a protein, but may be involved in regulating the expression of COL6A4P1.

Each of the collagen type 6 genes encodes for a small piece of the larger complex. As the individual components of the protein are made within cells, the collagen complex assembles in a complicated series of steps. Once assembled, the complex must be moved from the interior of the cell to the outside — a process called secretion or exocytosis. Outside of the cell, the completed collagen interacts with extracellular structural components — called the extracellular matrix or ECM — to form a bridge between cells and the surrounding connective tissue. This allows it to organize the three-dimensional architecture of tissues. Collagen type 6 is vital in the structure and function of skeletal muscles, tendons, bone, and cartilage. In muscles, collagen type 6 interacts with collagen type 4 and a protein called perlecan to bind muscle cells to the ECM.

UCMD and collagen type 6

Mutations in the COL6A1COL6A2, and COL6A3 genes have been associated with the development of UCMD. The mutations can cause problems with the interactions between collagen type 6 and its binding partners in the ECM, meaning that muscle cells are not anchored as they should in the connective tissue.

Sometimes, mutations in these genes may make the collagen type 6 components difficult to assemble. In such cases, not enough collagen type 6 is secreted. In general, mutations that cause less collagen type 6 to be produced are associated with more severe forms of the disease.

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