Opitz G / BBB syndrome ... (Opitz G / BBB syndrome) - Gen MID1.  

Opitz syndrome G / BBB is a genetic disease that affects several structures along the body midline.

The most frequent features of this disorder include hypertelorism, defects in the larynx, trachea and / or esophagus causing dysphagia and respiratory problems and hypospadias in males. Less than 50 percent of those affected have mild intellectual disabilities, most likely caused by structural defects in the brain. About half of the affected individuals also have cleft lip with or without cleft palate. Other features include heart defects, anal orifice obstruction and brain defects such as the absence of tissue that connects the left and right halves of the brain. Affected individuals have facial abnormalities such as a flat nasal bridge, thin upper lip, and low ears. These characteristics vary among affected individuals, even within the same family.

This process is due to mutations in the gene MID1, located on the short arm of chromosome X (Xp22). This gene encodes a protein called midina. This protein helps regulate the function of microtubules that form the structural framework of the cell. Microtubules help cells to maintain their shape, contribute to the process of cell division, and are essential for transporting material within cells. As part of its function degrading, protein is responsible for breaking an enzyme called protein phosphatase-2A (PP2A). This enzyme activates several proteins associated with microtubules.

There are more than 40 mutations in the gene in people with MID1 Opitz G / BBB linked to X. Most of these mutations change a single amino acid in the protein midina syndrome. Other mutations include deletions or insertions over an amino acid mutations and splice site, which causes the protein to be assembled incorrectly. All these mutations cause the midina not function properly attached to microtubules and cleaving PP2A. As a result, the PP2A protein accumulates in the cells. An excess of this protein altered abnormally functions associated proteins to microtubules, which in turn can affect its normal function. It is unclear how these changes interfere with normal development and cause birth defects associated with the syndrome. It is thought that a non - functional midina affects how cells divide and are associated along the midline of the body during development, resulting in many of the observed anomalies.  

Opitz syndrome G / BBB is often a dominant inheritance pattern X - linked, meaning that a copy of an altered gene in each cell is sufficient to cause disease. An alteration is considered X - linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In most cases, men have more obvious symptoms of the disease than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. In some cases, an affected person inherits a mutation from an affected parent MID1. Other cases may result from new mutations in this gene, which occur in people with no history of disease in your family.

Researchers have also described an autosomal dominant form of Opitz G / BBB caused by a deletion in one copy of chromosome 22 in each cell syndrome. In some cases, an affected person inherits a chromosome deletion of a parent segment. Other cases are the result of a deletion that occurs during the formation of reproductive cells or early fetal development. These cases occur in people with no history of disease in your family.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Opitz G / BBB, by complete PCR amplification of the exons of the gene MID1 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).