RECQL4

The RECQL4 gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA. Because RecQ helicases maintain the structure and integrity of DNA, they are known as the "caretakers of the genome."

Although the structure of the RECQL4 protein is similar to other members of the RecQ helicase family, it does not appear to act as a helicase within cells. The exact function of the RECQL4 protein is unknown. Like other RecQ helicases, however, this protein helps maintain the stability of each cell's genetic information and is important for normal DNA replication and repair.

The RECQL4 protein is active in several types of cells, both before and after birth. Researchers believe that this protein is particularly important in cells of the developing bones and skin. It has also been found in enterocytes, which are cells that line the intestine and absorb nutrients.

Baller-Gerold syndrome - caused by mutations in the RECQL4 gene

Several mutations in the RECQL4 gene have been identified in people with Baller-Gerold syndrome. Most of these mutations prevent cells from producing any RECQL4 protein or change the way the protein is pieced together, which disrupts its usual function. A shortage of this protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. It is unclear how these changes result in the varied signs and symptoms of Baller-Gerold syndrome, including the abnormal fusion of certain skull bones (craniosynostosis), small stature, missing thumbs or bones in the forearm (radial ray malformations), and a skin rash.

Rothmund-Thomson Syndrome - caused by mutations in the RECQL4 gene

More than 25 mutations in the RECQL4 gene have been found in people with Rothmund-Thomson syndrome. These mutations likely prevent the cell from producing any RECQL4 protein or lead to the production of an abnormally short, nonfunctional version of the protein. A shortage of this protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. Further study is needed to determine how these changes result in the characteristic features of Rothmund-Thomson syndrome, which include a skin rash, sparse hair, small stature, skeletal abnormalities, and an increased risk of certain cancers.

other disorders - caused by mutations in the RECQL4 gene

Mutations in the RECQL4 gene also cause a condition known as RAPADILINO syndrome. This disorder affects many parts of the body, and has signs and symptoms that overlap with those of Baller-Gerold syndrome and Rothmund-Thomson syndrome. The condition's varied features include radial ray malformations, malformed or missing kneecaps (patellae), an opening in the roof of the mouth called a cleft palate, diarrhea, dislocated joints, short stature, limb malformations, and a slender nose.

Most people who have been diagnosed with RAPADILINO syndrome are of Finnish descent. They have an RECQL4 mutation known as a splice-site mutation, which causes the RECQL4 protein to be pieced together incorrectly. This genetic change, which is written as IVS7+2delT, results in the production of a protein that is missing a region called exon 7. It is unknown how this faulty version of the RECQL4 protein leads to the signs and symptoms of RAPADILINO syndrome.