Lissencephaly , X - linked with abnormal genital (X-linked lissencephaly With abnormal genitalia) - Gen ARX.
X - linked lissencephaly with abnormal genitalia (XLAG) is a disease that affects brain development and genitals. This disease occurs more frequently in males and is characterized by abnormal brain development resulting in lissencephaly. People without folds in the brain (agiria) tend to have more intense than people with small folds and furrows (pachygyria) symptoms. Abnormalities in the brain can cause profubdo mental retardation and developmental delay, spasticity, hypotonia and feeding difficulties. Other features of the disease include agenesis of the corpus callosum, epilepsy, micropenis, cryptorchidism or ambiguous genitalia. Additional signs and symptoms include chronic diarrhea, transient hyperglycemia and problems regulating body temperature. Most children do not survive beyond infancy.
This disease is due to mutations in the ARX gene, located on the short arm of chromosome X (Xp21.3). This gene encodes a protein that is involved in the development of various organs, including the brain, testis and pancreas. In the developing brain, the protein is involved in the movement and communication between neurons. Protein regulates genes that play a role in migration of neurons to their proper location. In the pancreas and testes, protein helps regulate the process by which cells mature to perform specific functions.
Have identified at least 30 ARX gene mutations can cause X - linked lissencephaly with abnormal genitalia (XLAG). Mutations in the gene result encoding a nonfunctional protein or the complete absence of protein. As a result, the protein can not perform its function of regulating the activity of important genes for interneuron migration. In addition to harming normal brain development, lack of functional protein alters cell differentiation during the formation of the testes, leading to the development of abnormal genitalia. It is believed that altering protein function in the pancreas plays a role in chronic diarrhea and hyperglycemia in people with the disease. Women with a mutation in the ARX gene tend to have less overt signs and symptoms than men. Affected women may have agenesis of the corpus callosum, some degree of intellectual disability and epilepsy. Some women with a mutation of the gene do not experience symptoms.
Lissencephaly , X - linked inherited abnormal genital with X - linked pattern A disease is X - linked, if the mutated gene is the cause on the X chromosome, one of the two sex chromosomes in each cell . In males, an altered copy of the gene in each cell is sufficient to cause disease. In women, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to less severe brain malformations or may not cause symptoms. 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 lissencephaly , X - linked with abnormal genital, by complete PCR amplification of exons ARX 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).