19p13.13 deletion syndrome ... (19p13.13 deletion syndrome) - Genes best2, CACNA1A, CALR, MAST1, NFIX and Chromosome 19
19p13.13 deletion syndrome is a process due to a chromosomal rearrangement in which a small segment of chromosome 19 in each cell is removed. The deletion occurs in the short arm of chromosome 19 in the position p13.13.
This process is associated with certain features including macrocephaly, tall and severe to moderate intellectual disability. Many affected individuals show a significant delay in development, including speech. Certain symptoms such as hypotonia and ataxia, contribute to delays in motor development. Other additional signs and symptoms may include seizures, abnormalities of brain structure, and slight differences in facial features (for example, a prominent forehead). Many affected individuals have problems with feeding and digestion, including constipation, diarrhea, vomiting and abdominal pain. In addition, certain eye problems are common which can affect vision as strabismus and underdevelopment of the optic nerves. Signs and symptoms of 19p13.13 deletion syndrome vary among affected individuals. In part, this variation is that the size of the deletion, and the number of genes that are affected, varies from person to person.
People with 19p13.13 deletion syndrome have a deletion of about 300 kb to over 3 Mb in the short arm of chromosome 19. The deleted region occurs in the short arm of chromosome in p13.13 position, although some publications refer to it as p13.2. The region is the same; only the numbering differs. The exact size of the deletion affected varies among individuals, but is believed to include at least 16 genes. This deletion affects one of the two copies of chromosome 19 in each cell. Signs and symptoms of 19p13.13 deletion syndrome are due to loss of multiple genes in the deleted region. It is believed that some of these genes play an important role in normal growth and development, and the loss of one copy of each of these genes probably underlies the developmental delay, intellectual disability, and the other features of this entity . For example, studies suggest that deletion of CACNA1A (voltage-gated calcium channel alpha1 subunit A), may lead to seizures in affected individuals. Other genes affected in some people with 19p13.13 deletion syndrome may include best2 (bestrophin 2), CALR (calreticulin), MAST1 (microtubule associated serine / threonine kinase 1) and NFIX (nuclear factor IX) genes.
The best2 gene (bestrophin 2), located on the short arm of chromosome 19 (19p13.2), is a member of the family of genes bestrophin channel anions. This gene is primarily expressed in the retinal pigment epithelium and colon. The bestrophin genes share a similar genetic structure with highly conserved exon-intron limits but with different 3 'ends. The bestropinas are transmembrane proteins that contain a homologous region rich in aromatic residues, including an invariant arg-phe-motive pro.
The CACNA1A (voltage-gated calcium channel alpha1 subunit A) gene, located on the short arm of chromosome 19 (19p13), encoding the alpha-1 subunit of a calcium channel Cav2.1 called. This subunit forms the hole through which calcium ions can flow. These channels, transport of calcium ions across cell membranes and plays a key role in the ability of a cell to generate and transmit electrical signals. Calcium ions are involved in various cellular functions including cell-cell communication, muscle contraction and regulation of certain genes. It is believed that Cav2.1 channels are also implicated in the survival of neurons and the ability of these cells to change and adapt over time. Studies suggest that loss of one copy of CACNA1A can be the basis of seizures and ataxia in affected individuals. Suppression reduces the amount of Cav2.1 channels produced inside cells, although it is unclear exactly how these channels deficiency is related to ataxia and seizures in people with 19p13.13 deletion syndrome.
The CALR gene (calreticulin), located on the short arm of chromosome 19 (19p13.13), encoding calreticulin protein. This protein is found in various parts of the cell, including inside the endoplasmic reticulum (ER), cytoplasm, and cell outer surface. ER is involved in the processing and transport proteins, and inside this structure, calreticulin ensures the proper folding of proteins newly formed. The ER is also a storage location for calcium ions, and calreticulin is involved in maintaining the correct concentrations of calcium ions in the structure. Through the regulation of calcium and other mechanisms, it is believed that calreticulin exercises control of gene activity and proliferation, migration, adhesion and cell apoptosis. The function of this protein is important for immune system function and wound healing.
The MAST1 (microtubule associated serine / threonine kinase 1) gene, located on the short arm of chromosome 19 (19p13.2) encodes a protein binds dystrophin / utrophin microtubule network filaments through synthrophins.
The NFIX gene (nuclear factor IX), located on the short arm of chromosome 19 (19p13.3), encoding a protein transcription factor that binds to the palindromic sequence 5'-3'-TTGGCNNNNNGCCAA in cellular and viral promoters. The protein encoded may also stimulate replication of adenovirus in vitro. Described three transcript variants encoding different isoforms for this gene.
19p13.13 deletion syndrome usually not inherited , but develops as a result of a deletion of a chromosomal segment during the formation of reproductive cells or early embryonic development. Most affected people have no history of the disease in his family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with chronic benign pemphigus, by complete PCR amplification of the exons of Best2, CACNA1A, CALR, MAST1, NFIX, respectively, and subsequent sequencing genes.
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).