Juvenile polyposis syndrome ... (Juvenile polyposis syndrome) - Genes SMAD4 and BMPR1A
Juvenile polyposis, also known as juvenile polyposis syndrome, is a disease characterized by the presence of gastrointestinal polyps that develop during the first or second decade of life, with high potential for the development of cancers, and sometimes manifests other congenital anomalies. Patients with juvenile polyposis have at least 3 to 5 polyps, but may eventually develop hundreds, mainly in the colon, but can affect the rest of the gastrointestinal tract. Many individuals may be asymptomatic, although some have certain symptoms such as abdominal pain, anemia, diarrhea, bleeding and, in some cases, intussusception.
Individuals affected by juvenile polyposis are at high risk of developing pancreatic and gastric cancer, small bowel, colorectal. In fact, some authors point out that 21% of those affected by juvenile polyposis will develop colorectal cancer before age 34 years and 68% will do so before the age of 60 years old. In the 10 to 20% of cases of juvenile polyposis extraintestinal anomalies as Polydactyly, Malrotation, Meckel diverticulum, hydrocephalus, macrocephaly, Hypertelorism, heart defects and alterations are detected in the genitals.
Juvenile polyposis has been classified in three categories according to their phenotypic characteristics: 1) Juvenile polyposis coli, which polyps affect only the colon; 2) Juvenile polyposis Children (JPI), often fatal, characterized by diarrhea, bleeding, protein losing enteropathy and rectal prolapse; and 3) Juvenile polyposis widespread in which the polyps affect the colon, stomach and small intestine.
Juvenile polyposis is due to alterations in the sequence of SMAD4 genes located on the long arm of chromosome 18 (18q21.1) and BMPR1A, located on the long arm of chromosome 10 (10q22-q23). These genes encode proteins which are involved in the transmission of chemical signals from the cell membrane to the nucleus. This type of signaling pathway allows the environment outside the cell affect the way in which the cell encodes other proteins. The BMPR1A and SMAD4 proteins act together to help regulate the activity of particular genes, and growth and cell proliferation.
They have identified 60 mutations in the SMAD4 gene in individuals with juvenile polyposis syndrome. Most of these genetic mutations result encoding an abnormally short, nonfunctional protein. Deficiency or absence of functional protein SMAD4 inhibits binding to other proteins SMAD and interferes with the transmission of chemical signals from the cell surface to the nucleus. SMAD complex proteins is not activated and can not be transported to the cell nucleus where it is needed to regulate cell proliferation and activity of certain genes. This uncontrolled cell growth can lead to the formation of polyps in people with juvenile polyposis syndrome. In the described gene BMPR1A 60 mutations responsible for this process. As mutations in the SMAD4, most mutations result BMPR1A gene encoding an abnormally short, nonfunctional protein. Consequently, BMPR1A protein can not bind to the ligands in the TGF-? pathway. This disruption interferes with the binding of activation protein complex SMAD, that the nucleus, where it is needed to regulate cell growth and activity of certain genes is not transported. Uncontrolled cell growth can cause the formation of polyps in people with juvenile polyposis.
Juvenile polyposis syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the alteration. In approximately 75% of cases, an affected person inherits the mutation from an affected parent. The remaining 25% of cases are due to 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 juvenile polyposis syndrome, by complete PCR amplification of the exons of SMAD4 and BMPR1A, respectively, and subsequent sequencing genes.
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).