Коккейн синдромы: Сирек кездесетін және өлімге алып келетін генетикалық ауру

Cockayne syndrome (CS), also called Neill Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosensitivity), eye disorders and premature aging. Failure to thrive and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are other very common features. The underlying disorder is a defect in a DNA repair mechanism. Unlike other defects of DNA repair, patients with CS are not predisposed to cancer or infection. Cockayne syndrome is a rare but destructive disease usually resulting in death within the first or second decade of life. The mutation of specific genes in Cockayne syndrome is known, but the widespread effects and its relationship with DNA repair is yet to be well understood. Neill Dingwall syndrome was named after Mary M. Dingwall and Catherine A. Neill. The central and peripheral nervous systems progressively degenerate until death in the first or second decade of life as a result of serious neurological degradation. Cortical atrophy is less severe in CS Type I.
CS Type II is present from birth (congenital) and is much more severe than CS Type 1. Typically patients with this early onset form of the disorder show more severe brain damage, including reduced myelination of white matter, and more widespread calcifications, including in the cortex and basal ganglia.

If hyperoxia or excess oxygen occurs in the body, the cellular metabolism produces several highly reactive forms of oxygen called free radicals. This can cause oxidative damage to cellular components including the DNA. In normal cells, our body repairs the damaged sections. In the case of this disease, due to subtle defects in transcription, children's genetic machinery for synthesizing proteins needed by the body does not operate at normal capacity. Over time, went this theory, results in developmental failure and death. Every minute, the body pumps 10 to 20 liters of oxygen through the blood, carrying it to billions of cells in our bodies. In its normal molecular form, oxygen is harmless. However, cellular metabolism involving oxygen can generate several highly reactive free radicals. These free radicals can cause oxidative damage to cellular components including the DNA. In an average human cell, several thousand lesions occur in the DNA every day. Many of these lesions result from oxidative damage. Each lesion—a damaged section of DNA—must be snipped out and the DNA repaired to preserve its normal function. Unrepaired DNA can lose its ability to code for proteins. Mutations also can result. These mutations can activate oncogenes or silence tumor suppressor genes. According to research, oxidative damage to active genes is not preferentially repaired, and in the most severe cases, the repair is slowed throughout the whole genome. The resulting accumulation of oxidative damage could impair the normal functions of the DNA and may even result in triggering a program of cell death (apoptosis). The children with this disease do not repair the active genes where oxidative damage occurs. Normally, oxidative damage repair is faster in the active genes (which make up less than five percent of the genome) than in inactive regions of the DNA. The resulting accumulation of oxidative damage could impair the normal functions of the DNA and may even result in triggering a program of cell death (apoptosis).