ERCC6

More than 60 ERCC6 gene mutations that cause Cockayne syndrome have been identified. This rare condition includes a variety of features, including an abnormally small head size (microcephaly), very slow growth resulting in short stature, delayed development, and an increased sensitivity to sunlight (photosensitivity).

Many of the ERCC6 gene mutations that cause Cockayne syndrome lead to the production of an abnormally short version of the CSB protein that cannot function properly. Other mutations change single building blocks (amino acids) in the CSB protein, which also results in a malfunctioning protein.

The mechanism by which ERCC6 gene mutations lead to Cockayne syndrome is not well understood. The altered CSB protein probably hinders DNA repair and may be unable to assist with gene transcription. As a result, damaged DNA is not fixed, which disrupts gene transcription and prevents the normal production of proteins. These abnormalities impair cell function and eventually lead to the death of cells in many organs and tissues. Faulty DNA repair underlies photosensitivity in affected individuals, and researchers suspect that it also contributes to the other features of Cockayne syndrome. It is unclear how ERCC6 gene mutations cause all of the varied features of this condition.

At least one mutation in the ERCC6 gene can cause UV-sensitive syndrome, a condition characterized by unusual sensitivity to UV rays from the sun. People with UV-sensitive syndrome sunburn easily and have freckled skin or other changes in skin coloring (pigmentation). The known mutation, which is written as Arg77Ter or R77X, replaces the amino acid arginine with a premature stop signal at position 77 in the CSB protein. If any protein is produced, it is abnormally short and quickly broken down. Without this protein, skin cells cannot repair DNA damage caused by UV rays, and transcription of damaged genes is blocked. However, it is unclear how a loss of the CSB protein causes UV-sensitive syndrome. Additionally, it is unknown why the Arg77Ter mutation causes photosensitivity without the other features of Cockayne syndrome (described above).

MedlinePlus Genetics provides information about Age-related macular degeneration