Cartilage-hair hypoplasia (Cartilage-hair hypoplasia) - Gen RMRP.

Cartilage hypoplasia - hair is a disorder characterized by bone growth dwarfism other skeletal abnormalities, hypotrichosis and immunodeficiency. Signs and symptoms of the disease include unusually short stature limbs from birth, metaphyseal chondrodysplasia, difficulties for the full extension of the arms, hair lighter, sparse and thin color other family members, hypopigmentation, nail misshapen and dental anomalies.

It is considered that people affected with severe immune problems have severe combined immunodeficiency (SCID). These people have virtually no immune protection to bacteria, viruses and fungi, and are prone to repeated and persistent infections that can be serious or life threatening. These infections are usually caused by organisms "opportunists" who usually do not cause disease in people with normal immune systems. Most people with hypoplastic cartilage - hair, even those with an immune mild deficiency, have respiratory infections, ear and sinuses. In particular, the chickenpox virus often causes serious infections in people with the disease. Affected individuals also have a higher risk of developing cancer, especially basal cell carcinomas, leukemia and lymphoma. Additionally, there may be gastrointestinal problems such as inability to absorb nutrients or celiac disease. Affected individuals may have Hirschsprung's disease, an intestinal disorder that causes severe constipation, intestinal obstruction and enlargement of the colon. In addition, the disease can cause anal stenosis and esophageal atresia.

This disease is due to mutations in the gene RMRP, located on the short arm of chromosome 9 (9p21 - p12). Unlike many genes, the gene encodes a molecule RMRP called antisense RNA. This molecule binds to several proteins, forming an RNase-MRP enzyme. It is believed that l RNase-MRP enzyme is involved in several important processes in the cell. For example, it is likely to assist in the copy of the DNA found in the mitochondria, in ribosomal RNA processing is required for the assembly of amino acids in proteins and functional control the cell cycle d.

There are more than 50 mutations in the gene RMRP causing disease. Approximately 90% of cases of this disorder are caused by a mutation in which the guanine nucleotide is replaced by the adenine nucleotide at position 70 in the RMRP (70A> G) gene. It is likely that mutations in the gene give rise to encoding an antisense RNA that is unstable. This unstable molecule can not bind to some of the proteins necessary to form the complex enzyme RNase-MRP. S and believes that these changes affect the activity of the enzyme, which interferes with its important functions within cells. Interruption of RNase-MRP complex enzyme cause low dwarfism, skeletal abnormalities, immunodeficiency, increased risk of cancer, hypotrichosis and other signs and symptoms of cartilage hypoplasia - hair.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with cartilage hypoplasia - hair, by complete PCR amplification of exons RMRP 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).