Coats plus syndrome ... (plus Coats syndrome) - Gen CTC1

Coats plus syndrome is a hereditary disorder characterized by an ocular condition called Coats disease with abnormalities , brain, bone, gastrointestinal and other body parts. Coats disease affects the retina and causes blood vessels in the retina are excessively dilated and twisted, causing fluid loss, which can eventually cause retinal detachment, which can lead to loss of vision. Individuals with this syndrome also have brain abnormalities, including abnormal calcium deposits, the development of cysts and loss of cerebral white matter (leukodystrophy). These brain abnormalities worsen over time, causing slow growth, movement disorders, convulsions and reduced intellectual function.

Other features of the syndrome include osteopenia, which makes bones fragile and break easily, as well as anemia, accompanied by unusually pale skin and extreme tiredness. Affected individuals may also have serious or life threatening complications, including gastrointestinal bleeding and portal hypertension. Less common features plus Coats syndrome may include thinning hair prematurely gray, malformations of the fingernails and toenails, and abnormalities of the skin, such as cafe au lait spots.

Syndrome Coats plus and a condition called leukoencephalopathy with calcifications and cysts (LCC, or Labrune syndrome), sometimes have been grouped under the generic term microangiopathy cerebroretinal with calcifications and cysts (CRMCC) because they have very similar brain abnormalities. However, Coats plus syndrome and LCC have different genetic causes, and are generally described as separate instead of variants of a single alteration processes.

The CTC1 gene, located on the short arm of chromosome 17 (17p13.1), CTC1 encoding protein which plays an important role in telomere, which are at the ends of chromosomes, which correspond to repetitive DNA segments that help protect the chromosomes to prevent sticking together or degrade. In most cells, the telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that causes the cell to stop dividing and self - destruct. The CTC1 protein acts as part of a group of proteins known as the CST complex, which is involved in telomere maintenance. This resort is part of the special machinery that cells use to copy some telomeres so they do not become too short as cells divide. CTC1 is suggested that the protein may also intervene in DNA replication unrelated to the telomere, but these functions are not well understood.

They have identified at least 20 mutations in the gene in affected CTC1 people with Coats plus syndrome. Most affected individuals have a mutation in one copy of the gene in every cell CTC1 eliminating function CTC1 protein and a mutation in the other copy of the gene that reduces but does not eliminate protein function. This combination of mutations leaves only a small amount of protein functional CTC1 available to work as part of complex CST. Deterioration of this complex affects telomere replication, although the effect on the structure and function of telomeres is unclear. Some studies have found that people with genetic mutations in the gene CTC1 have abnormally short telomeres, while other studies have found no change in telomere length.

This disease 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 syndrome Coasts plus, by complete PCR amplification of the exons of the gene CTC1, 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).