Frontometaphyseal dysplasia (Frontometaphyseal dysplasia) - Gen FLNA.
Frontometaphyseal dysplasia is a disorder that causes abnormal development of the skeleton and other health problems. This disease is one of related disorders referred otopalatodigital spectrum disorders that also includes otopalatodigital syndrome type 1, type 2 and the otopalatodigital syndrome syndrome Melnick-Needles. Overall, these changes involve loss of hearing due to malformations in the bones of the ears, problems in the development of the palate and skeletal abnormalities involving the fingers.
Frontometaphyseal dysplasia is distinguished from other disturbances otopalatodigital spectrum by the presence of contractures restricting the movement of some joints. Other signs and symptoms include scoliosis, abnormalities of the fingers and hands, prominent brow ridges, slanted eyes down, micrognathia and small, missing or misaligned teeth. Some people affected with hearing loss. In addition to skeletal abnormalities, individuals with frontometaphyseal dysplasia may have obstruction of the ureters, heart defects, or constrictions in the bronchi that can lead to respiratory problems. Overall, affected males have signs and symptoms of more serious than women, who may have only the characteristic facial features disease.
This process is due to mutations in the gene FLNA, located on the long arm of chromosome X (Xq28). This gene codes filamin protein A. This protein binds to another protein called actin and helps form the branched network of filaments forming the cell cytoskeleton. Filamin A also binds actin with many other proteins to perform various functions within the cell, including regulation of skeletal development and brain, the formation of blood vessels and blood clotting.
Has identified a small number of mutations in exons 4, 22, 29, 33, and 44 to 46 in the FLNA gene in people with dysplasia frontometaphyseal. These mutations appear to increase the activity of filamin A or grant a new atypical protein function. It is believed that mutations can change the way filamin. However, it is unclear how changes in the protein are associated with specific signs and symptoms of frontometaphyseal dysplasia.
This disease is inherited as a dominant X - linked pattern because the gene associated with this change is on this chromosome. In women, a mutation in one of the two copies of the gene in each cell is sufficient to cause disease. In males, a mutation in the single gene copy in each cell causes alteration. In most cases, men have more severe 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.
Tests in IVAMI: in IVAMI perform detection of mutations associated with frontometaphyseal dysplasia, by complete PCR amplification of the exons of the gene FLNA, and subsequent sequencing.