Mutations in genes STN1 cause Coats, plus - syndrome
A team of Israeli researchers has discovered that mutations in STN1, a gene that helps maintain the ends of chromosomes, cause rare, inherited disorder and Coats syndrome. The study "mutations cause Coats STN1 and the syndrome and are associated with genomic defects and telomeres," will be published online before publication in July 18 The Journal of Experimental Medicine .
and Coats syndrome affects many body tissues, including the eye, brain, bone marrow and the gastrointestinal tract. the disease is a telomeropathy known to be caused by mutations in the gene encoding CTC1, a protein that helps maintain telomere structures called that protect the ends of chromosomes. If the telomeres are not maintained properly, the cells lose their ability to divide and chromosomes can fuse together.
Directed by Gideon Raz Somech Rechavi and Central and Sara Sheba medical Selig Rambam Health Care Campus and the Technion Institute, the researchers identified two Palestinian Coats and patients who do not have mutations in the gene CTC1. Instead, patients carried mutations in the gene encoding STN1, a protein that functions in conjunction with CTC1 and another protein, Ten1 to maintain telomeres. Cells isolated from patients had dysfunctional telomere and a decreased ability to divide.
To confirm that mutations in STN1 were the cause of the coats and the patients' symptoms, the researchers, in collaboration with David Wiest of the Fox Chase Cancer Center, has knocked out the equivalent gene in fish embryos zebra. The coats of most developed fish-like symptoms engineering, including a lack of red blood cells and the formation of expansion, fragmented blood vessels. This last symptom has been corrected using thalidomide, a potent inhibitor of blood vessel formation.
The researchers report that one of the two patients died as a result of massive gastrointestinal bleeding. However, they were able to partially control the gastrointestinal bleeding of the second patient using thalidomide, which shows a success "approach to bed bed-and-back." The researchers now plan to study exactly how mutations in STN1 cause patient symptoms. In addition to maintaining telomeres, the protein complex of DNA replication CTC1-STN1-Ten1 auxiliaries on the whole genome, a process that is also defective in cells of patients. "How many features can be attributed to telomere or genome-wide replication defects, or other non-replicating DNA defects are still exploring," the researchers say.
and Coats syndrome affects many body tissues, including the eye, brain, bone marrow and the gastrointestinal tract. the disease is a telomeropathy known to be caused by mutations in the gene encoding CTC1, a protein that helps maintain telomere structures called that protect the ends of chromosomes. If the telomeres are not maintained properly, the cells lose their ability to divide and chromosomes can fuse together.
Directed by Gideon Raz Somech Rechavi and Central and Sara Sheba medical Selig Rambam Health Care Campus and the Technion Institute, the researchers identified two Palestinian Coats and patients who do not have mutations in the gene CTC1. Instead, patients carried mutations in the gene encoding STN1, a protein that functions in conjunction with CTC1 and another protein, Ten1 to maintain telomeres. Cells isolated from patients had dysfunctional telomere and a decreased ability to divide.
To confirm that mutations in STN1 were the cause of the coats and the patients' symptoms, the researchers, in collaboration with David Wiest of the Fox Chase Cancer Center, has knocked out the equivalent gene in fish embryos zebra. The coats of most developed fish-like symptoms engineering, including a lack of red blood cells and the formation of expansion, fragmented blood vessels. This last symptom has been corrected using thalidomide, a potent inhibitor of blood vessel formation.
The researchers report that one of the two patients died as a result of massive gastrointestinal bleeding. However, they were able to partially control the gastrointestinal bleeding of the second patient using thalidomide, which shows a success "approach to bed bed-and-back." The researchers now plan to study exactly how mutations in STN1 cause patient symptoms. In addition to maintaining telomeres, the protein complex of DNA replication CTC1-STN1-Ten1 auxiliaries on the whole genome, a process that is also defective in cells of patients. "How many features can be attributed to telomere or genome-wide replication defects, or other non-replicating DNA defects are still exploring," the researchers say.
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