What are the genetic changes related to Rothmund-Thomson syndrome ?
Mutations in the RECQL4 gene cause about two-thirds of all cases of Rothmund-Thomson syndrome. This 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. The RECQL4 protein helps stabilize genetic information in the body's cells and plays a role in replicating and repairing DNA.  RECQL4 mutations lead to the production of an abnormally short, nonfunctional version of the RECQL4 protein or prevent cells from making any of this protein. A shortage of the RECQL4 protein may prevent normal DNA replication and repair, causing widespread damage to a person's genetic information over time. It is unclear how a loss of this protein's activity leads to the specific features of Rothmund-Thomson syndrome.  In about one-third of individuals with Rothmund-Thomson syndrome, no mutation in the RECQL4 gene has been found. The cause of the condition in these individuals is unknown; however, researchers suspect that these cases may result from mutations in a gene related to the RECQL4 gene.  In some cases, chromosomal abnormalities have been identified in people with Rothmund-Thomson syndrome. These abnormalities include extra or missing genetic material, usually from chromosome 7 or chromosome 8, in some of an affected person's cells. Researchers believe that these chromosomal changes arise because of the overall instability of an affected person's genetic information; they do not cause the disorder.