Atelosteogenesis Type 3 (atelosteogenesis type 3) - Gen FLNB.
Atelosteogenesis type 3 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, hands and feet wide, camptodactilia or syndactyly. In addition, these individuals have characteristic facial features including a broad forehead, hypertelorism and a nose underdeveloped. About half of affected individuals have cleft palate.
Often, individuals with type 3 atelosteogenesis have an underdeveloped ribcage affecting the development and lung function. As a result, these individuals generally stillborn or die shortly after birth due to respiratory failure. Some affected individuals survive longer with intensive medical support. These individuals have more respiratory problems due to the weakness of the airways that can cause a partial closure, apnea or frequent infections. People with atelosteogenesis type 3 who survive beyond the neonatal period may have learning disabilities, delayed language skills and delayed development of motor skills, probably due to low oxygen levels in the brain as a result of respiratory problems.
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.
Have identified at least six genetic mutations in FLNB in people with type atelosteogenesis 3. These mutations change individual amino acids in the protein filamin B or eliminate a small section of the protein sequence, resulting in an abnormal protein. This abnormal protein appears to have a new atypical function that interferes with normal proliferation or differentiation of chondrocytes, deteriorating ossification and causing the signs and symptoms of type 3 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 3 by the complete PCR amplification of 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).