Cherubism (Cherubism) - Gen SH3BP2.  

Cherubism is a disorder characterized by the presence of abnormal bone tissue at the bottom of the face. From early childhood, the lower and upper jaw enlarged with increasing cysts painless. These growths give a swollen cheeks rounded appearance and often interfere with the normal development of teeth. In some people the disease is so mild, it may not be noticeable, while other cases are severe enough to cause problems with vision, breathing, speech and swallowing. The enlargement of the jaw usually continues throughout childhood and stabilizes during puberty. When growth is abnormal, gradually replaces normal bone in early adulthood.

Most people with this condition have few signs and symptoms affecting other parts of the body. Rarely, however, this alteration occurs as part of another genetic disorder. For example, the cherubism may occur in Ramon syndrome, also it implies a short, mental retardation, and gingival fibrosis. Additionally, cherubism has been reported in rare cases of Noonan (a developmental disorder characterized by unusual facial features, short stature, and heart defects) syndrome and the X fragile syndrome (a disorder that primarily affects men that causes learning disabilities and cognitive impairment).

This process is due in 80 percent of people, to mutations in the gene SH3BP2, located on the short arm of chromosome 4 (4p16.3). In most other cases, the genetic cause of the disease is unknown. This gene encodes a protein whose exact function is not clear. The protein plays a role in the transmission of chemical signals within cells, in particular cells involved in bone remodeling and certain immune system cells.

They have identified at least 11 mutations in the gene causing SH3BP2 cherubism. Each of these mutations changing one amino acid in a critical region of the protein, with the synthesis of an active protein, which probably disrupts signaling pathways critical associated with maintenance of bone tissue and in some cells of the immune system cells . It is likely to cause protein overactive inflammation in the jaw bones and triggers the production of osteoclasts. An excess of these bone cells contribute to the destruction of bone in upper and lower jaws. A combination of bone loss and inflammation, probably underlies the growths as characteristic cherubism cysts.

This alteration is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from an affected parent. Other cases result from 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 Cherubism, by complete PCR amplification of exons SH3BP2 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).