Prader-Willi syndrome ..., (Prader-Willi syndrome) - Gen OCA2 and chromosome 15.

The Prader-Willi syndrome is a complex genetic disorder that affects many parts of the body. In childhood, it characterized by hypotonia, feeding difficulties, poor growth and developmental delay. From childhood, affected individuals develop an insatiable appetite, leading to hyperphagia and obesity. Some people with Prader-Willi syndrome, particularly those with obesity also develop diabetes mellitus type 2. Other signs and symptoms associated may include mild to moderate mental retardation, learning disabilities, behavioral problems and sleep disturbances. In addition, those affected have characteristic features such as a narrow forehead, almond - shaped eyes, triangular face, short stature, small hands and feet, unusually pale skin and light colored hair. Affected men and women affected have underdeveloped genitals. Puberty is delayed or incomplete, and the people most affected are sterile.

The Prader-Willi syndrome is due to loss of function of genes in a particular region of chromosome 15. Normally, people inherit a copy of this chromosome from each parent. Some genes are activated only on the paternal copy. This activation of specific genes is due to genomic imprinting. About 70% of cases of Prader-Willi syndrome occurs when a segment of paternal chromosome 15 is deleted in each cell. People with this chromosomal change present absence of certain critical genes in this region because the genes are eliminated in the paternal copy, and the copy genes in human are inactive. In another 25% of cases, a person with Prader-Willi syndrome has two copies inherited maternal chromosome 15 instead of a copy of each parent, a phenomenon known as maternal uniparental disomy. Rarely, the Prader-Willi Syndrome can also be due to translocation, or a mutation or other defect that becomes abnormally inactive genes in the paternal chromosome 15.

It seems likely that the characteristic features of Prader-Willi syndrome are due to loss of function of several genes on chromosome 15. Among them, those genes encoding snoRNAs. These molecules have a variety of functions, including contributing to regulate other types of RNA molecules. It is likely that the loss of a particular group of snoRNA genes, known as the cluster SNORD116, can play an important role in the cause of the signs and symptoms of the disease. However, it is not clear how the absence of SNORD116 could contribute to intellectual disabilities, behavioral problems and physical characteristics of the disease.

In some people with Prader-Willi loss OCA2, located on the long arm of chromosome 15 (15q), it is associated with unusually clear skin and light colored hair. However, the loss of OCA2 gene does not cause the other signs and symptoms of the disease. The protein encoded by this gene, called P protein helps determine skin pigmentation, hair and eyes. This protein is found in melanocytes. Although the exact function of the P protein is unknown, it is essential for normal pigmentation and is likely to be involved in the production of melanin. Within melanocytes, P protein can transport molecules into and out of melanosomes. Furthermore, it is likely that this protein may also help regulate the pH of melanosomes.

Most cases of Prader-Willi syndrome are not inherited, especially those due to a deletion in the paternal chromosome 15 or maternal UPD. These genetic changes occur randomly during the formation of reproductive cells or early embryonic development. Usually, people affected have no history of the disease in his family. Rarely, genetic change responsible for Prader-Willi syndrome can be inherited. For example, it is possible that an abnormally inactivating genes on chromosome 15 paternal genetic change is transmitted from one generation to the next.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Prader-Willi syndrome by genetic study of OCA2 and chromosome 15.

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).