Cockayne Syndrome
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What is Cockayne syndrome?Cockayne syndrome is a rare disorder characterized by short stature and an appearance of premature aging. Features of this disorder include a failure to gain weight and grow at the expected rate (failure to thrive), small head size (microcephaly), impaired development of the nervous system, and an abnormal sensitivity to sunlight (photosensitivity). Other possible signs and symptoms include hearing loss, eye abnormalities, severe tooth decay, and problems with internal organs. Cockayne syndrome can be divided into subtypes, which are distinguished by the severity and age of onset of symptoms. Classical, or type I, Cockayne syndrome is characterized by an onset of symptoms in early childhood (usually after age 1 year). Cockayne syndrome, type II is an early-onset form with severe symptoms that are apparent at birth (congenital). Type II Cockayne syndrome is sometimes called cerebro-oculo-facio-skeletal (COFS) syndrome or Pena-Shokeir syndrome type II. A few cases of type III Cockayne syndrome, which has mild symptoms and onset in late childhood, have been reported. Some individuals have combined features of Cockayne syndrome and another photosensitivity disorder called xeroderma pigmentosum, which is characterized by a wide range of skin changes, from mild freckling to skin cancer. How common is Cockayne syndrome?The prevalence of Cockayne syndrome is unknown. It probably occurs in fewer than 1 in 100,000 individuals. What genes are related to Cockayne syndrome?Mutations in the ERCC6 and ERCC8 genes cause Cockayne syndrome. The ERCC6 and ERCC8 genes provide instructions for making proteins that are involved in repairing damaged DNA. If either gene is altered, DNA damage is not rapidly repaired. As a result, damaged DNA accumulates, which probably leads to impaired cell functions and eventually, cell death. Increased cell death likely contributes to features of Cockayne syndrome such as growth failure and premature aging. How do people inherit Cockayne syndrome?This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.
Source: National Institutes of Health
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Findings from Tokyo Medical and Dental University broaden understanding of cancer gene therapy
2007 FEB 26 -- Research findings, "Knockdown of XAB2 enhances all-trans retinoic acid-induced cellular differentiation in all-trans retinoic acid-sensitive and -resistant cancer cells," are discussed in a new report. "Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is composed of 855 amino acids, contains 15 tetratricopeptide repeat motifs, and associates with Cockayne syndrome group A and B proteins and RNA polymerase II, as well as XPA. In vitro and in vivo studies showed that XAB2 is involved in pre-mRNA splicing, transcription, and transcription-coupled DNA repair, leading to preimplantation lethality, and is essential for mouse embryogenesis," scientists writing in the journal Cancer Research report. "Retinoids are effective for the treatment of preneoplastic diseases including xeroderma pigmentosum and other dermatologic diseases such as photoaging. We therefore focused on defining the effect of XAB2 on cellular differentiation in the presence of ATRA treatment. In the present study, we showed that overexpression of XAB2 inhibited ATRA-induced cellular differentiation in human rhabdomyosarcoma cell line, and that knockdown of XAB2 by small interfering RNA (siRNA) increased ATRA-sensitive cellular differentiation in the human promyelocytic leukemia cell line HL60 at both physiologic (10(-9)-10(-8) mol/L) and therapeutic (10(-7) mol/L) concentrations of ATRA. Moreover, we found that XAB2 was associated with retinoic acid receptor alpha (RARalpha) and histone deacetylase 3 in the nuclei. Finally, using siRNA against XAB2, we showed that the ATRA-resistant neuroblastoma cell line IMR-32 underwent cellular differentiation induced by ATRA at a therapeutic concentration (10(-6) mol/L)," wrote K. Ohnuma-Ishikawa and colleagues, Tokyo Medical and Dental University. The researchers concluded: "These results strongly suggest that XAB2 is a component of the RAR corepressor complex with an inhibitory effect on ATRA-induced cellular differentiation and that XAB2 plays a role in ATRA-mediated cellular differentiation as an important aspect of cancer therapy." Ohnuma-Ishikawa and colleagues published their study in Cancer Research (Knockdown of XAB2 enhances all-trans retinoic acid-induced cellular differentiation in all-trans retinoic acid-sensitive and -resistant cancer cells. Cancer Research, 2007;67(3):1019-29). Additional information can be obtained by contacting K. Ohnuma-Ishikawa, Graduate Medical School, Dept. of Pediatrics, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 11308519, Japan. The publisher of the journal Cancer Research can be contacted at: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA. Keywords: Japan, Tokyo, Biotechnology, Cancer Gene Therapy, Cancer Research, Ichthyosis, Oncology, Xeroderma Pigmentosum. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
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