Jacobsen syndrome ...; 11q deletion terminal; 11 q deletion syndrome of ..., (Jacobsen syndrome) - Genes ARHGAP32, ETS1, FLI1 and chromosome 11


Jacobsen syndrome is a disease contiguous gene with congenital anomalies multiple / mental retardation (MCA / MR) due to a partial deletion of the long arm of chromosome 11. Because of this deletion occurs at the end of the long arm of chromosome 11 , Jacobsen syndrome also known as altering the terminal 11q deletion or 11q deletion syndrome.

Signs and symptoms of Jacobsen syndrome vary considerably. Individuals most affected may show delayed development, including the development of motor skills and speech, learning difficulties, cognitive impairment, behavioral problems, short attention span and easy distraction. Many people with Jacobsen syndrome have been diagnosed with attention deficit disorder and hyperactivity disorder (ADHD). In addition, Jacobsen syndrome is also associated with an increased risk of autism spectrum disorders. In addition, affected individuals have distinctive facial features, such as small low-set ears, hypertelorism, ptosis, skin folds covering the inner corner of the eyes in epicanto, a broad nasal bridge, corners of the mouth down, a lip thin upper and a small lower jaw. Often, affected individuals have macrocefalia and trigonocephaly called cranial anomaly, which gives the front a pointed look.

More than 90 percent of people with Jacobsen syndrome has a coagulation disorder called Paris-Trousseau of which causes a risk of bleeding lifelong syndrome and bruising easily. Other characteristics of Jacobsen syndrome may include heart defects, feeding difficulties in childhood, short, frequent ear infections, and skeletal abnormalities. In addition, this syndrome can also affect the digestive system, kidneys and genitals. The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood.

Jacobsen syndrome is due to a deletion of genetic material at the end of the long arm of chromosome 11. The deletion size varies between individuals affected, although most affected individuals have a deletion of 5Mb to 16Mb. In almost all those affected, suppression includes the end of chromosome 11. The larger deletions tend to cause signs and smaller deletions more severe symptoms. The features of Jacobsen syndrome are likely related to the loss of multiple genes on chromosome 11. Depending on its size, the absent region may contain about 170 to over 340 genes. Although many of these genes have not been identified, the genes in this region appear to be critical for normal development of many parts of the body, including the brain, facial features, and heart. Only a few genes have been studied as potential contributors to the specific characteristics of Jacobsen syndrome.

The ARHGAP32 gene (Rho GTPase activating protein 32), located on the long arm of chromosome 11 (11q24.3), encodes a protein GTPase activation associated neurons can regulate dendritic morphology and participate in cell differentiation during the formation of neuronal extensions of neurons.

The ETS1 gene (proto-oncogene ETS 1 transcription factor), located on the long arm of chromosome 11 (11q23.3), encodes a member of the family of ETS transcription factors, which are defined by the presence of a conserved domain ETS DNA binding that recognizes the core consensus DNA sequence GGAA of / T in the target genes. These proteins act either as transcriptional activators or repressors of numerous genes and are involved in the development of stem cell senescence and cell death, and carcinogenesis. It can control the differentiation, survival and proliferation of lymphoid cells. You can also regulate angiogenesis by regulating the expression of genes controlling migration and invasion of endothelial cells.

FLI1 (Fli-1 proto-oncogene, transcription factor ETS), located on the long arm of chromosome 11 (11q24.1-q24.3), encodes the synthesis of FLI protein that controls gene transcription. Transcription is the first step in the process of protein coding. The FLI protein is part of a group of related proteins, called transcription factor family ETS. Protein aggregates (FLI) bind to certain regions of DNA and activate transcription of nearby genes. The proteins encoded from these genes control many important cellular processes such as growth, proliferation, differentiation and cell survival. FLI protein is mainly in blood cells and is thought to regulate their development.

Most cases of Jacobsen syndrome are not inherited, but are due to a chromosomal deletion occurs as a random event during the formation of reproductive cells or early embryonic development. Affected individuals often have no history of the disease in your family, even though they can transmit the deletion of chromosome to their children. Between 5 and 10% of people with Jacobsen syndrome inherit the chromosomal abnormality of an affected parent. In these cases, the parent carries a balanced translocation, in which a segment of chromosome 11 has been exchanged with a segment of another chromosome. In a balanced translocation, it is not won or lost genetic material. Balanced translocations usually do not cause any health problems; however, they may become unbalanced as they are transmitted to the next generation. Children who inherit an unbalanced translocation may have a chromosomal rearrangement absently genetic material and extra genetic material. Individuals with Jacobsen syndrome who inherit an unbalanced translocation have an absence of genetic material from the end of the long arm of chromosome 11 and have additional genetic material from another chromosome. These chromosomal changes result in health problems characteristic of this syndrome.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Jacobsen syndrome, by complete PCR amplification of the exons of the ARHGAP32, ETS1 and FLI1 genes, 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).