Cockayne syndrome ... (Cockayne syndrome) - Genes ERCC6 and ERCC8  

Cockayne syndrome is a rare condition characterized by microcephaly, retardation of growth and developmental delay. Signs and symptoms of this condition are usually evident from infancy, and worsen over time. Most affected individuals have photosensitivity, and in some cases even a small amount of sun exposure can cause burns or blisters on the skin. Other common signs and symptoms include hearing loss, vision loss, tooth decay, bone abnormalities, hands and feet are cold continuously, and changes in the brain that can be seen on brain scans. Individuals with syndrome Cockayne display a severe reaction drug metronidazole. If affected individuals taking this drug, you can provoke a potentially fatal liver failure.

Cockayne syndrome sometimes divided into types I, II, and III based on the severity and the age of onset of symptoms. However, the differences between the types are not always clear, and some authors suggest that the signs and symptoms rather reflect a spectrum of different types. The type II Cockayne syndrome is also known as cerebro-oculo-facio-skeletal syndrome (SCWO), and while some researchers consider it a separate but similarly affected, others classified as part of the spectrum of Cockayne syndrome.

This may be due to mutations in the gene ERCC6 (Excision Repair ERCC 6, chromatin remodeling factor), located on the long arm of chromosome 10 (10q11.23), or mutations in the gene ERCC8 (ERCC excision repair 8 CSA ubiquitin I ligase complex subunit), located on the long arm of chromosome 5 (5q12.1). These genes encode proteins (CSB and CSA, respectively) that are involved in the repair of damaged DNA. DNA can be damaged by ultraviolet (UV) and toxic chemicals, radiation and free radicals. Cells are usually able to correct DNA damage before it causes problems. If not corrected, DNA damage accumulates, which causes cells have malfunctioned and can cause cell death. Although DNA damage occurs frequently, cells are generally able to fix it before it can cause problems.

The cells have several mechanisms to correct DNA damage. One of these mechanisms involve the CSA and CSB proteins. These proteins are specialized in repair of damaged inside DNA active genes (those genes undergoing gene transcription). When DNA is damaged in active genes, enzyme holding gene transcription (RNA polymerase) and the process stops crashes. It is believed that the enzyme helps remove CSB RNA polymerase damaged site, so that DNA can be repaired. CBS protein can also help restart gene transcription after the damage is corrected. The specific role of the CSA protein in this process is unclear. CSA is likely that the protein interacts with other proteins to identify areas of damaged DNA.

They have identified 60 mutations ERCC6 genes and more than 30 genetic mutations in people with ERCC8 Cockayne syndrome. Many of these mutations result in the synthesis of an abnormally short version of CBS or CSA protein can not function properly. Other mutations change specific amino acids in the CSB or CSB protein, which also translates into a protein malfunctioning. Although the mechanism by which mutations in genes ERCC8 ERCC6 and result in the syndrome Cockayne not well understood, it is likely that the altered proteins hinder DNA repair and may be unable to help with gene transcription. As a result, damaged DNA interrupted gene transcription and inhibits normal protein synthesis. These anomalies alter cell function and can lead to death of cells in many organs and tissues. Defective DNA repair causes photosensitivity in affected individuals, and is believed to also contribute to the other features of Cockayne syndrome.

This syndrome is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Cockayne syndrome, by complete PCR amplification of the exons of ERCC6 and ERCC8 genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).