Potocki-Shaffer syndrome ...; 11P proximal deletion (Potocki-Shaffer syndrome) - Genes EXT2, ALX4 and phf21a


The Potocki-Shaffer syndrome, also known as proximal 11p deletion syndrome is a disorder that affects the development of bones, brain and other organs. Signs and symptoms of Potocki-Shaffer syndrome vary widely among individuals affected and may include multiple exostosis or osteochondromatosis, enlarged parietal foramina that are "soft spots" in the head, mental retardation and delayed language development, motor skills and social skills. Many people affected have characteristic facial features such as a large skull, brachycephaly, a prominent forehead, bridge of the narrow nose, short philtrum and mush mouth. Less commonly, the disease can lead to vision problems, additional skeletal abnormalities and defects in the heart, kidneys and urinary tract.

Syndrome Potocki-Shaffer is due to a deletion of genetic material on the short arm of chromosome 11 at 11p11.2 position. The size of the deletion varies among affected individuals. Studies suggest that the full spectrum of characteristics is a consequence of a deletion of at least 2.1 million base pairs of DNA. The loss of multiple genes within the deleted region causes the signs and symptoms of Potocki-Shaffer syndrome. In particular, the removal of EXT2, ALX4, and phf21a genes associated with some of the characteristic features of Potocki-Shaffer syndrome. Studies indicate that loss of EXT2 gene is associated with the development of osteocondromas in affected individuals. ALX4 suppressing gene leads to enlarged parietal foramina. Phf21a loss gene is the cause of mental retardation and distinctive facial features. The loss of additional genes in the deleted region probably contributes to the other features of Potocki-Shaffer syndrome.

The EXT2 (exostosin glycosyltransferase 2) gene, located on the short arm of chromosome 11 (11p12-p11) encoding exostosina-2 protein. This protein is found in the Golgi apparatus, which modifies newly encoded enzymes and other proteins. In the Golgi apparatus, aggregates exostosina-2 bind to another protein, exostosina-1 to form a complex that modifies the protein to heparan sulfate that can be used by the body. The heparan sulfate is involved in the regulation of a variety of body processes including angiogenesis and blood clotting. Also it has a role in metastasis of cancer cells. In individuals with Potocki-Shaffer syndrome of a mutation leads to suppression of the EXT2 gene. This loss of EXT2 gene is responsible for multiple exostosis and generates a reduction exostosina-2 proteins and inability to process correctly heparan sulfate. Although the heparan sulfate is involved in many processes in the body, it is not clear how this protein deficiency causes multiple exostoses. The loss of another gene, ALX4, in the same region of chromosome 11 underlying the developmental defects of the skull.

The gene ALX4 (ALX homeobox 4), located on the short arm of chromosome 11 (11p11.2), encodes a protein that is a member of the homeobox family of proteins. These proteins direct the formation of body structures in early embryonic development. Protein is necessary for normal development of the head and face, particularly the formation of the nose. This protein is also involved in forming skin layers, but its role in this process is poorly understood. The protein is a transcription factor that controls the activity of genes that regulate the growth, proliferation and migration, ensuring that the cells grow and stop growing at specific times and that are positioned correctly during development. A mutation causing the deletion of the gene results ALX4 Potocki-Shaffer syndrome. In people with this disease, a loss of ALX4 gene on the short arm of chromosome 11 is responsible for the enlarged parietal foramina. This feature is a result of a deficiency transcription factor ALX4 because gene deletion alters several cellular processes and impairs ossification.

The phf21a (PHD finger protein 21A) gene, located on the short arm of chromosome 11 (11p11.2), encoding a protein involved in histone demethylation, which helps regulate gene activity. Histones are structural proteins that bind to DNA and chromosomes shape. Removing a methyl group of histones (histone demethylation), it helps to silence certain genes. Studies indicate that the protein binds phf21a histones that have been demethylated to maintain demethylated histone genes and silenced. The phf21a protein appears to be particularly important in the regulation of genes involved in neuronal development and facial. In people with Potocki-Shaffer syndrome, a genetic change that causes suppression phf21a gene is responsible for mental retardation and distinctive facial features. Suppression probably results in a reduction in the amount of protein phf21a. It is believed that the disruption resulting from the demethylation of histones alters the activity of genes involved in neuronal and facial development, leading to mental retardation and distinctive facial features.

The Potocki-Shaffer syndrome follows an autosomal dominant pattern of inheritance, which means that a deletion of genetic material from one copy of chromosome 11 is enough to express the disease. However, this condition may be hereditary or may occur as a result of a new chromosome change. In some cases, an affected person inherits a chromosome deletion from a parent segment. Most often, the disease is due to a deletion that occurs during the formation of reproductive cells in utero or early fetal development. These cases occur in people with no history of disease in your family.

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Potocki-Shaffer, by complete PCR amplification of the exons of EXT2, ALX4 and phf21a, 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).