Burn-McKeown syndrome ... (Burn-McKeown syndrome) - Gen TXNL4A

Syndrome Burn-McKeown (BMKS), also known as "facial oculo-oto-dysplasia" or "bilateral choanal atresia, heart defects, deafness and dysmorphic aspect" is a congenital process associated with abnormalities of the nasal passages, features facial characteristic, hearing loss, heart abnormalities and short stature.

Signs and symptoms associated with Burn-McKeown syndrome may include: bilateral choanal stenosis or bilateral choanal atresia, which can cause potentially fatal respiratory problems in childhood; characteristic facial features such as palpebral fissures, coloboma in the lower eyelids, hipertelorismo, philtrum, microstomia and prominent ears; sensorineural hearing loss and conductive hearing loss; short stature; and congenital, such cardiac defects as patent ductus arteriosus (PDA). Intelligence is not affected in the Burn-McKeown syndrome.

This process is due to mutations in the gene TXNL4A (like thioredoxin 4A), or the promoter region of TXNL4A gene regulating protein synthesis from the gene. The TXNL4A gene, located on the long arm of chromosome 18 (18q23), encodes a subunit of a protein complex called the main spliceosome, which is the main spliceosome of the two types found in human cells. The spliceosomes introns identified and removed to help produce mature mRNA molecules from immature mRNA molecules.

They have identified at least 10 genetic mutations in people with TXNL4A Burn-McKeown syndrome. Most people with Burn-McKeown syndrome have a different genetic change in each of the two copies of the gene in every cell TXNL4A, a situation known as composite heterozygosity. In a copy of the gene, the mutation results in a protein with impaired function, or inhibits protein synthesis. TXNL4A the other copy of the gene has a deletion of a small amount of genetic material in the promoter region of TXNL4A gene, which regulates protein - coding of that gene. This genetic change reduces production of proteins. Studies suggest that a reduction in the amount of encoded proteins from gene affects TXNL4A main spliceosome assembly and change the production of a particular group of mRNA molecules; however, the details of these changes and their relationship to specific signs and symptoms of Burn-McKeown syndrome are unknown. It has been shown that mutations in several genes involved in spliceosome lead to the development of craniofacial malformations, because it is believed that craniofacial development is particularly sensitive to problems spliceosome.

This disease is inherited in an autosomal recessive pattern, which means that 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 syndrome Burn-McKeown (BMKS), by complete PCR amplification of exons TXNL4A 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).