Chromosome 17
Duplication of 17q12 is a chromosomal change that operates in all cells of the body causing intellectual disability, developmental delay and a wide range of physical abnormalities, although many individuals may not present with disorders, even being members of the same family. Most people with duplications of 17q12 have an additional copy of approximately 1.4 Mb of DNA at position q12 on chromosome 17. This chromosomal segment is prone to reorganize during cell division, which can lead to additional or missing copies. of DNA in 17q12.
Acute promyelocytic leukemia is caused by a translocation of genetic material between chromosomes 15 and 17. This translocation, written as t (15; 17), fuses part of the PML gene of chromosome 15 with part of the RARA gene of chromosome 17. It is a mutation. of somatic character. The translocation t (15; 17) is called a balanced reciprocal translocation because the pieces of the chromosome exchange with each other (reciprocal) and no genetic material is gained or lost. The PML gene on chromosome 15 provides instructions for a protein that acts as a tumor suppressor, which means that it prevents cells from growing and dividing too quickly or uncontrollably. The PML protein blocks cell growth and division (proliferation) and induces self-destruction (apoptosis) in combination with other proteins. As a result, blood cells get stuck in the promyelocyte stage and proliferate abnormally. Excess promyelocytes accumulate in the bone marrow and normal white blood cells cannot form causing the disease.
Charcot-Marie-Tooth disease is caused by the duplication of a small piece of chromosome 17 at the p12 position that includes the PMP22 gene. Charcot-Marie-Tooth disease damages the peripheral nerves, which connect the brain and spinal cord with muscles and sensory cells that detect sensations such as touch, pain, heat and sound. Peripheral nerve damage can cause alteration or loss of sensation and atrophy of the muscles of the feet, legs and hands. The protein produced by the PMP22 gene is a component of myelin, vital for the proper functioning of the nervous system. The extra copy of the PMP22 gene resulting from duplication leads to an overproduction of PMP22 protein; It is assumed that the excess of this protein can overwhelm the ability of cells to process it correctly.
Dermatofibrosarcoma protuberan, is a rare skin cancer caused by the translocation of genetic material between chromosomes 17 and 22, t (17; 22). This translocation fuses part of the COL1A1 gene on chromosome 17 with part of the PDGFB gene on chromosome 22. The translocation is found in one or more additional chromosomes that can be linear or circular (rings). This anomaly promotes an excess of PDGFB protein, which in turn abnormally stimulates cells to proliferate and differentiate, which leads to the formation of tumors seen in dermatofibrosarcoma protuberans. It is a rare type of infiltrating soft tissue sarcoma, usually with a low degree of malignancy, that leaves the skin's dermis. The prevalence is estimated at 1 in 10,000, and the annual incidence around 1 in 200,000. DFSP can occur at any age, including childhood and childhood, although it usually occurs between the second and fifth decade of life. Between 85 and 90% of these tumors constitute low-grade lesions, and the rest are high-grade and fibrosarcomatous (FS) type lesions. The lesions usually present as a noisy erythema in the form of reddish or pink violet plaque or, well, as a nodular mass in the trunk, proximal extremities or head and cervical region. Its growth tends to be slow, along with local infiltrations into deeper tissues, as well as a propensity for local recurrence after excision.
Koolen-de Vries syndrome is due to the removal of a small amount of genetic material on chromosome 17. This disorder is characterized by developmental delay, intellectual disability, a cheerful and sociable disposition and a variety of physical abnormalities such as hypotonia or epilepsy. Most people with Koolen-de Vries syndrome lack a sequence of approximately 500,000 base pairs, (500 kb), at position q21.31 on chromosome 17. The exact size of the deletion varies among individuals. affected, but contains at least six genes, including KANSL1. This removal affects one of two copies of chromosome 17 in each cell.
While Koolen-de Vries syndrome is generally not inherited, most people with the condition have had at least one parent with a common variant of region q21.31 of chromosome 17. This variant is found in 20 One hundred of people of European and Middle Eastern descent, although rare in other populations. In the H2 lineage, a 900 kb DNA segment, which includes the region removed in most cases of Koolen-de Vries syndrome, has undergone an inversion. Although investment is very common, only an extremely small percentage of parents with the investment have a child affected by Koolen-de Vries syndrome.
Miller-Dieker syndrome is caused by a removal of genetic material near the end of the short (p) arm of chromosome 17. The signs and symptoms of Miller-Dieker syndrome are related to the loss of multiple genes in this region, particularly the called PAFAH1B1, it is responsible for the characteristic sign of lissencephaly syndrome, a problem with brain development in which the surface of the brain is abnormally smooth. This brain abnormality causes severe intellectual disability, developmental delay, seizures, abnormal muscle stiffness (spasticity), or weak muscle tone (hypotonia) and feeding difficulties. The loss of another gene, called YWHAE, in the same region of chromosome 17 increases the severity of lissencephaly in people with Miller-Dieker syndrome. Additional genes in the deleted region contribute to the varied characteristics of this disorder.
Potocki-Lupski syndrome is the result of a duplication of a small piece of chromosome 17, specifically a region of the short arm (p) designated p11.2. This condition is characterized by a developmental delay, mild to moderate intellectual disability, behavioral problems, including autism spectrum disorder, sleep disorders and other health problems.
Although the duplicated region contains multiple genes, researchers believe that having an additional copy of a particular gene, RAI1, underlies many of the characteristic features of Potocki-Lupski syndrome. The RAI1 gene provides instructions to produce a protein that helps regulate the activity (expression) of other genes; among them, those involved in daily (circadian) rhythms, such as the sleep-wake cycle. Too much RAI1 protein can also disrupt brain development, which could explain developmental delay, intellectual disability, behavioral problems and other neurological features of this condition. The development of bones in the head and face may also be affected, which leads to subtle facial differences in people with Potocki-Lupski syndrome.
Smith-Magenis syndrome is usually the result of a deletion of a small piece of chromosome 17 in each cell, specifically a region of the short arm (p) designated as p11.2. This developmental disorder affects many parts of the body. The main features of this condition include mild to moderate intellectual disability, speech and language delay, distinctive facial features, sleep disorders and behavioral problems. Very often, the chromosomal segment removed in Smith-Magenis syndrome is the same as that duplicated in Potocki-Lupski syndrome. The signs and symptoms of Smith-Magenis syndrome are thought to be due to the RAI1 gene since all people presenting with the syndrome are involved.
Yuan-Harel-Lupski syndrome (YUHAL) is due to the duplication of a small portion of chromosome 17 in the p12-11.2 region; It is characterized by multiple neurological problems similar to those of Potocki-Lupski syndrome (described above) and CMT1A. In YUHAL syndrome, the duplicated segment varies in size from approximately 3 Mb to almost 20 Mb and always contains the RAI1 and PMP22 genes; It can also include additional genes. Certain characteristics of YUHAL syndrome, such as developmental delay and behavioral problems, are probably caused by an additional copy of the RAI1 gene. It is likely that other characteristics, such as muscle weakness and decreased sensitivity to touch, heat and cold in the lower legs and feet, are due to duplication of the PMP22 gene.
Cancer. Changes in chromosome 17 have been identified in several types of cancer, these are somatic mutations. A particular chromosomal abnormality called isocromosome 17q occurs frequently in some types of cancer. This abnormal version of chromosome 17 has two long arms (q) instead of one long and one short (p). As a result, the chromosome has an extra copy of some genes and copies of other genes are missing. An isochromosome 17q is commonly found in a blood-forming tissue cancer called Chronic myeloid leukemia (CML). It has also been identified in certain solid tumors, including a type of brain tumor called medulloblastoma and tumors of the brain and spinal cord known as primitive neuroectodermal tumors. At the moment the specific mechanisms that trigger cancer are unknown.
Other changes in the number or structure of chromosome 17 can have a variety of effects, including intellectual disability, delayed development, characteristic facial features, weak muscle tone (hypotonia) and short stature. These changes include an additional piece of chromosome 17 in each cell (partial trisomy 17), a missing segment of the chromosome in each cell (partial monosomy 17) and a circular structure (ring).
