Coffin-Lowry syndrome ... (Coffin-Lowry syndrome) - Gen RPS6KA3
The Coffin-Lowry syndrome is a disorder that affects many parts of the body. Signs and symptoms are usually more severe in men than in women, although women affected the characteristics of this syndrome range from very mild to severe. Men with Coffin-Lowry syndrome have moderate to profound mental retardation and developmental delay. Affected women may be cognitively normal, or may have intellectual disabilities from mild to profound. Beginning in childhood or adolescence, some people with this condition have brief episodes of syncope when excited or startled by a loud noise. These episodes are known as drop episodes induced by stimuli.
Most affected males and some women affected, have characteristic facial features, including a prominent forehead, widely spaced eyes and tilted down, short nose with a wide tip and a wide mouth with full lips. These features become more pronounced with age. Hands have short and tapered fingers. Additional features include short stature, microcephaly, kyphoscoliosis and other skeletal abnormalities.
Mutations Coffin-Lowry syndrome of are in the RPS6KA3 gene, located on the short arm of chromosome X (Xp22.2-p22.1). This gene encodes a protein that is part of a family called ribosomal S6 kinases (RSKs) which are involved in signaling within cells. RSK is believed that proteins play a role in several important cellular processes, including cell growth and division, cell specialization and apoptosis. In addition, it is believed that this protein helps control the activity of other genes and plays an important role in the brain. The protein is involved in cell signaling pathways required for learning, memory and long term survival of nerve cells.
They have identified more than 125 mutations in the gene RPS6KA3 in people with Coffin-Lowry Syndrome of. All these mutations reduce or eliminate the activity of the protein RPS6KA3. Some mutations inserted or deleted gene in the genetic material or change the instructions to encode the protein gene. Other mutations change the amino acids in the protein RPS6KA3. These genetic mutations result in the synthesis of little or no protein RPS6KA3; however, it is unclear how the deficiency or absence of this protein causes the symptoms of Coffin-Lowry syndrome. RPS6KA3 functional protein seems to be important for learning and memory, but its role in the skeleton is unknown. In some people with the characteristics of Coffin-Lowry syndrome they have not been identified mutations in the gene RPS6KA3. In these cases, the cause of the condition is unknown.
They have identified mutations in the gene RPS6KA3 in some people with intellectual disabilities, but they do not have most of the other characteristics of Coffin-Lowry syndrome. Because the RPS6KA3 gene is on the X chromosome, this disorder is known as mental retardation X - linked
The Coffin-Lowry syndrome is inherited as a dominant pattern linked to chromosome X. An alteration is considered X-linked if the mutated gene that results in the development of patrology is on the X chromosome, one of the two chromosomes sex. Inheritance is dominant if a copy of the altered gene in each cell is sufficient to express the condition. In most cases, males, who have one X chromosome in each cell, signs and symptoms more severe disease than women, who have two X chromosomes in each cell. A feature of the X-linked inheritance is that fathers can not pass X-linked traits to their sons chromosome. Between 70 and 80 percent of people with Coffin-Lowry syndrome have no history of the disease in their families. These cases are due to new mutations in the gene RPS6KA3. The remaining 20 to 30 percent of affected individuals have other family members with Coffin-Lowry syndrome.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Coffin-Lowry syndrome, by complete PCR amplification of the exons of the gene RPS6KA3, 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).