Interstitial lung surfactant deficiency, disease ... (Interstitial lung disease due to deficiency Surfactant; Surfactant dysfunction) - Genes ABCA3, SFTPB and SFTPC
Interstitial lung surfactant deficiency disease is a lung disorder that causes breathing problems. This disease results from changes in the composition or the function of pulmonary surfactant, a mixture of phospholipids and proteins that lines the lung tissue and eases breathing. Without regular surfactant, the tissue surrounding the alveoli adheres together after exhalation, causing the collapse of the alveoli. As a result, air filling the lungs with each breath is difficult, and the entry of oxygen to the body affected.
Signs and symptoms of the disease can vary in intensity. The most severe form of the disease causes respiratory distress syndrome in newborns, in which they have great difficulty breathing and can not get enough oxygen. Lack of oxygen can damage the brain and other organs of the newborn. This syndrome leads to respiratory failure, and most infants with this condition do not survive more than a few months. Less severe forms have a gradual onset of respiratory problems in children or adults, and have abnormally rapid breathing, low oxygen concentrations in blood and growth retardation.
There are several types of the disease, identified by their genetic cause. One type, called SP-B deficiency, causes respiratory distress syndrome in newborns. Other types, known as SP-C deficiency and deficiency ABCA3 have signs and symptoms ranging from mild to severe.
This process is due to mutations in one or more of the ABCA3, SFTPB and SFTPC genes.
The ABCA3 gene, located on the short arm of chromosome 16 (16p13.3), encoding a protein involved in surfactant production. This protein is found in the membrane surrounding the lamellar bodies, which are cellular structures in which the phospholipids and proteins that make up the surfactant are packaged. Protein transports phospholipids in lamellar bodies which interact with surfactant proteins to form the surfactant. The protein also appears to be involved in the formation of normal lamellar bodies. They have identified more than 100 genetic mutations in the gene ABCA3 causing disease. These mutations lead to the reduction or absence of protein function, without which the transport of phospholipids surfactant decreases. In addition, the formation of lamellar bodies deteriorates. These changes can cause serious breathing problems, often fatal in newborns.
The SFTPB gene, located on the short arm of chromosome 2 (2p12-p11.2), encodes a protein called surfactant protein B (SP-B). Protein SP-B helps spread the surfactant through the surface of lung tissue, to lower the surface tension of the surfactant. Surfactant proteins must pass through several stages of processing to mature and become functional. Protein SP-B plays a role in the formation of lamellar bodies and therefore affects processing of a protein called surfactant-surfactant protein C (SP-C). They have identified more than 30 mutations in the gene cause the disease SFTPB. These mutations lead to partial or complete loss of mature SP-B, resulting in abnormal surfactant composition and a decrease in surfactant function. In addition, the formation of lamellar bodies deteriorates. Lack of normal lamellar bodies leads to abnormal processing of SP-C, resulting in a reduction of mature SP-C and an accumulation of unprocessed forms of SP-C. Functional loss of the surfactant increases the surface tension in the alveoli, causing difficulty in breathing and lung collapse.
The SFTPC gene, located on the short arm of chromosome 8 (8p21), encodes a protein called Surfactant C (SP-C). This protein is one of the four proteins (each produced from a different gene) of the surfactant. They have identified more than 35 mutations in the gene cause the disease SFTPC. These changes affect processing of SP-C protein. Many of the mutations occur in a particular region of the gene , called the domain BRICHOS, which appears to be involved in processing and cell placement SP-C protein. Mutations in the gene cause a reduction SFTPC or absence of SP-C and mature accumulation of abnormal forms of SP-C. Immaturity SP-C can lead to abnormal surfactant composition and decreased surfactant function. Loss of functional surfactant increase the surface tension in the alveoli, causing difficulty in breathing and lung collapse. Moreover, it appears that the SP-C protein processed abnormally, accumulate within lung cells. These misfolded proteins can trigger a cellular response that causes cell damage and death. This damage can disrupt production and release of surfactant leading to respiratory problems associated with the disease.
Interstitial lung surfactant deficiency disease may have different patterns of inheritance depending on their genetic cause. When the disease is caused by mutations in genes SFTPB or ABCA3, this condition 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. When the disease is caused by mutations in the gene SFTPC, this condition has a pattern of autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause disease. In about half the cases caused by changes in gene SFTPC, an affected person inherits the mutation from an affected parent. The rest is the result of new mutations in the gene and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with interstitial lung surfactant deficiency disease, by complete PCR amplification of the exons of ABCA3, SFTPB and SFTPC respectively genes 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).