Christianson syndrome ... (Christianson syndrome) - Gen SLC9A6
Christianson syndrome is a process that primarily affects the nervous system that manifests in childhood. The characteristic features of Christianson syndrome include developmental delay, intellectual disability, inability to speak, ataxia, and difficulty to keep standing or walking. People who learn to walk lose this ability in childhood. The most affected children also have episodes of epilepsy beginning between the ages of 1 and 2 years. Other features seen in many people with Christianson syndrome include microcephaly; a long, narrow face with a nose, jaw and prominent ears; a mouth open with drooling; and abnormal eye movements. Children usually have a cheerful demeanor with frequent spontaneous smile and a laugh.
Christianson syndrome is due to mutations in the SLC9A6 gene (solute carrier family 9 member A6), located on the long arm of the X chromosome (Xq26.3), encoding the protein exchanger sodium / hydrogen 6 (Na + / H + 6 or NHE6). The Na + / H + exchangers found in the membranes surrounding the cells or compartments inside cells. Exchange of hydrogen ions helps to regulate the pH of the cell or cellular compartment. The NHE6 protein is found in the membrane of endosomes, which recycle proteins and other cellular materials. The NHE6 protein controls the pH within endosomes, which is important for the function of recycling these compartments. Furthermore, the protein can NHE6 have additional functions, such as protein trafficking.
Mutations in the SLC9A6 gene generally result in an abnormally short coding NHE6 protein which is nonfunctional or decomposes rapidly in cells, resulting in the absence of functional NHE6 channels. As a result, the pH in the endosomes is not maintained properly. It is unclear how a pH in the endosomes unregulated leads to neurological problems in people with Christianson syndrome. Some studies have shown that protein trafficking from endosomes is important for learning and memory, but the role of endosomal pH or NHE6 protein in this process has not been identified.
Christianson syndrome is inherited as a recessive X - linked pattern in males, who have only one X chromosome, an altered copy of the gene in each cell it is sufficient to express the disease. In females, having two X chromosomes, a mutation would have to occur in both copies of the gene for the disease is expressed. Because it is unlikely that women have two altered copies of this gene, males are affected by recessive X - linked disorders much more frequently than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. In X - linked recessive inheritance, a woman with a mutated copy of the gene in each cell is called a carrier. You can pass the altered gene, but usually shows no signs and symptoms of the disease. In some cases, however, women who carry a mutation in the SLC9A6 gene have mild learning difficulties. It is unclear whether these disabilities are related to gene mutation or occur by chance.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Christianson syndrome, by complete PCR amplification of exons SLC9A6 gene, 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).