Lujan syndrome ... (Lujan syndrome) - Gen MED12
Lujan syndrome is a process that almost exclusively affects males and is characterized by mental retardation, behavioral problems and certain physical characteristics.
Intellectual disability associated with Lujan syndrome is generally mild to moderate. Behavioral problems may include hyperactivity, aggression, extreme shyness and excessive demand for care. Some affected individuals have characteristics of autism or related to development affecting communication and social interaction disorders. In some individuals we have found psychiatric problems such as delusions and hallucinations. The characteristic physical features of Lujan syndrome include a tall, slender and macrocefalia body. Affected individuals also have a long, thin face with distinctive facial features such as a prominent nasal root, philtrum, narrow palate, and micrognathia crowded teeth. In addition, almost all people affected have hypotonia.
Other signs and symptoms may include additional abnormal speech, cardiac defects , and genitourinary. Many affected individuals have unusually long digits with hyperextensibility. Individuals have also been described with seizures and abnormalities of the corpus callosum.
The Lujan syndrome is due to alterations in the gene sequence MED12 (mediator complex subunit 12), located on the long arm of chromosome X (Xq13), encoding the subunit of interposer 12. As its name suggests, this protein is a subunit complex mediator, a group of about 25 proteins that act together to regulate gene activity. The complex binds mediator physically transcription factors with RNA polymerase II enzyme. Once transcription factors are linked, this enzyme initiates gene transcription, the process by which the information stored in the DNA of a gene is used to encode proteins. MED12 is believed that the protein is involved in many aspects of early development, including the development of neurons in the brain. The MED12 protein is part of several chemical signaling pathways within cells. These pathways help direct a wide range of cellular processes such as growth, migration, and differentiation activities.
It has identified at least one mutation in the MED12 gene responsible for the syndrome of Lujan. This mutation replaces the amino acid asparagine at the amino acid serine at position 1007 of MED12 (Asn1007Ser or N1007S) protein. The mutation alters the structure of the protein and probably MED12 its ability to regulate gene activity, but it is not known how these changes affect the development and give rise to the characteristics of Lujan syndrome.
This process 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.
Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Lujan, by complete PCR amplification of the exons of the gene MED12, 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).