Mental retardation , X - linked, Siderius (X-linked intellectual disability, Siderius type) type - Gen PHF8.

Mental retardation X - linked type Siderius is a disease characterized by mild to moderate intellectual disability that affects only males. Often, affected children show a delayed development of motor skills and have cleft lip and cleft palate. Some children and men affected have characteristic facial features, including elongated face, a sloping forehead, a broad nasal bridge, supraorbital ridge, oblique palpebral fissures up, low - set ears and big hands.

This process is due to mutations in the gene PHF8, located on the short arm of chromosome X (Xp11.22). This gene encodes a protein found in the cell nucleus, particularly in cells of the brain before and just after birth. The PHF8 protein is part of a group of proteins known as carriers zinc containing one or more domains makers zinc. These regions include a specific amino acid pattern and one or more zinc ions. The folded configuration of zinc finger domain stabilizes the protein and allowed to bind to other molecules. The PHF8 carrier protein domain contains a specific zinc called PHD domain, which binds to the complex of chromatin, the DNA and histones network joining DNA in chromosomes. Binding protein with PHF8 is part of chromatin remodeling. While protein PHF8 binds chromatin, another protein domain PHF8 called Jumonji C (JmjC), removes the methyl groups from histones. Demethylation causes chromatin is assembled freely and increases the expression of specific genes.

They have been described at least four mutations in the gene responsible PHF8 X - linked mental retardation Siderius type. Most mutations lead to an abnormally short protein is transported out of the cell nucleus. Outside the core, PHF8 protein can not interact with chromatin to regulate gene expression. Other mutations alter the ability of the protein to remove methyl groups from histones in the chromatin, which causes a decrease in gene expression. Although the exact mechanism of the disease is unknown, it is likely that the function of the altered protein or protein deficiency PHF8 in the nucleus of cells of the brain before birth, prevent chromatin remodeling, which alters the expression of genes involved in intellectual function and the formation of structures along the midline of the skull. This altered gene expression leads to intellectual disability and other characteristics of the disease.

This disease is inherited in a recessive X - linked pattern The associated gene is on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), an altered copy of the gene in each cell is sufficient to express the disease. In females, having two X chromosomes, a mutation would have to occur in both copies of the gene to express the disease. Because it is unlikely that women have two altered copies of this gene, males are affected by X - linked recessive 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.

Tests in IVAMI: in IVAMI perform detection of mutations associated with X - linked mental retardation Siderius type, by complete PCR amplification of the gene exons PHF8, 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).