Atelosteogenesis Type 1 (type 1 atelosteogenesis) - Gen FLNB.
Type 1 atelosteogenesis is a disorder that affects the bone development of the whole organism. Affected individuals are born with clubfoot and dislocations of the hip, knees and elbows. The bones of the spine, ribs, pelvis and extremities may be underdeveloped or, in some cases, absent. As a result of abnormalities in the bones of the extremities, people have very short arms and legs. On the other hand, the characteristic facial features include prominent forehead, hypertelorism a snub nose with a fluted tip and micrognatia. Additional features may include cleft palate and, in males, undescended testes.
Often, individuals with type 1 atelosteogenesis have an underdeveloped chest affecting the development and lung function. As a result, these individuals generally stillborn or die shortly after birth due to respiratory failure.
This process is due to mutations in the gene FLNB, located on the short arm of chromosome 3 (3p14.3). This gene encodes the protein filamin B. This protein helps constitute the cytoskeleton which gives structure to the cells and allows them to change shape and move. Filamin B is especially important in skeletal development before birth. This protein is expressed in chondrocytes. Furthermore, the protein appears to be important for normal cell growth and proliferation, differentiation of chondrocytes and cartilage ossification.
They have identified at least 7 gene mutations responsible FLNB atelosteogenesis type 1 gene mutation changing amino acids in the protein filamin B or remove a small part of the protein sequence, which results in an abnormal protein. This abnormal protein appears to have a new atypical function that interferes with proliferation or differentiation of chondrocytes, deteriorating ossification and leading to the signs and symptoms of type 1 atelosteogenesis.
This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for alteration is expressed. Almost all cases are caused by 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 atelosteogenesis type 1 by PCR amplification of complete exons FLNB 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).