Cri du chat syndrome ... (Cri-du-chat syndrome) - Gen CTNND2 and chromosome 5
Cri du chat syndrome, also called monosomy 5p (or 5p) and cri du chat, facial is a genetic disease characterized by mental retardation and developmental delay, low birth weight, hypotonia, microcephaly, dysmorphic ( hypertelorism, low - set ears, small jaw, rounded face) and high - pitched cry -for which called meowing cat. In addition, some affected children are born with a heart defect. However, the clinical picture is variable depending on the patient's age, there may be significant phenotypic differences.
The phenotypic variability own cri du chat syndrome is related to both the location and the extent of the deletion that originates, located on the short arm of chromosome 5 (5p15). From obtained cytogenetic and molecular studies of patients it has been established that the region responsible for the characteristic cry of this syndrome includes section 15.3 (5p15.3) and facial dysmorphism, microcephaly and intellectual disabilities are located in Section 15.2 (15p15.2). Deletion of the gene encoding telomerase reverse transcriptase, TERT - situated 5p15.33- could also contribute to heterogeneous phenotype cri du chat syndrome of. Work is underway to determine how the loss of other genes in this region contributes to the characteristic features of the syndrome.
The gene CTNND2, located on the short arm of chromosome 5 (5p15.2), coding for the protein delta-catenin. This protein is active in the nervous system, which is likely to contribute to cell adhesion and play a role in cell movement. In the developing brain, it can help in neuronal migration. In mature nerve cells, delta-catenin is in dendrites. Dendrites branch to the outside of the cell and receive information from nearby nerve cells. This information is transmitted via synapses, where delta-catenin appears to play a crucial role in their function.
Most cases result from large deletions that can include anything from a small segment of the short arm of chromosome 5 short arm whole. As a result of this deletion, many people affected have an absence of a copy of the gene CTNND2 in each cell. The loss of this gene can cause severe mental retardation in some affected individuals. It is believed that intellectual disability could be the result of altered neuronal migration in the early development of the nervous system. People with cri du chat syndrome who do not have a deletion of the gene CTNND2 often have mild intellectual disability or normal intelligence. Another type of genetic abnormalities, such as microdeletions, mosaicism and rings are fairly minor.
Most cases of cri du chat syndrome is not inherited. Elimination occurs most often as a random event during the formation of reproductive cells or early embryonic development, so affected individuals often have no history of the disease in his family. About 10% of people with cri du chat syndrome inherited chromosomal abnormality from an affected parent. In these cases, the parent carries a balanced translocation in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems, however, may become unbalanced as they are transmitted to the next generation. Children who inherit an unbalanced translocation may have a chromosomal rearrangement extra or missing genetic material. Individuals with cri du chat syndrome inherit an unbalanced translocation have an absence of genetic material on the short arm of chromosome 5, which leads to health problems and intellectual disabilities characteristic of this disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with cri du chat syndrome by complete PCR amplification of the exons of the gene CTNND2 and main regions affected in the region 5p15, 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).