CDKN1C

The CDKN1C gene provides instructions for making a protein that helps regulate growth. This protein acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. It also is involved in controlling growth before birth, preventing the developing fetus from becoming too large.

People inherit one copy of most genes from their mother and one copy from their father. For most genes, both copies are fully active, or "turned on," in cells. The CDKN1C gene, however, is most active when it is inherited from a person's mother. The copy of CDKN1C inherited from a person's father is active at much lower levels in most tissues. This sort of parent-specific difference in gene activation is caused by a phenomenon called genomic imprinting.

CDKN1C is part of a cluster of genes on the short (p) arm of chromosome 11 that undergo genomic imprinting. A nearby region of DNA known as imprinting center 2 (ICR2) or KvDMR controls the parent-specific genomic imprinting of CDKN1C and several other genes thought to help regulate growth.

Beckwith-Wiedemann syndrome - caused by mutations in the CDKN1C gene

At least half of all cases of Beckwith-Wiedemann result from changes in a process called methylation that affects the ICR2 region. In genes that undergo genomic imprinting, the parent of origin is often marked, or "stamped," on the gene during the formation of egg and sperm cells. This stamping process, called methylation, is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA.

In many people with Beckwith-Wiedemann syndrome, the ICR2 region has too few methyl groups attached (hypomethylation). This abnormality disrupts the regulation of several genes that are normally controlled by ICR2. Specifically, hypomethylation of the ICR2 region greatly reduces the activity of CDKN1C and neighboring genes. Because the CDKN1C gene normally restrains growth, a loss of the gene's activity leads to overgrowth, an increased risk of tumors, and the other features of Beckwith-Wiedemann syndrome.

In a few cases, Beckwith-Wiedemann syndrome has been caused by deletions of a small amount of DNA from the ICR2 region. Like abnormal methylation, these deletions disrupt the activity of several genes, including CDKN1C.

Beckwith-Wiedemann syndrome can also result from mutations within the CDKN1C gene itself. More than 15 mutations in this gene have been identified. These genetic changes alter the structure of the CDKN1C protein such that it can no longer control cell growth and division effectively. A loss of this protein leads to the growth problems characteristic of Beckwith-Wiedemann syndrome.