Effects of Mutations on Chromosome 17

Chromosome 17, like the other 22 pairs of chromosomes found in the human genome, plays a highly integral and important role in the development and growth of humans. There are an estimated 1,200 to 1,500 genes located on this specific pair that are involved in such biological functions from enzyme formation to protein synthesis and gene regulation. Unfortunately, mutations do occur with this chromosome. A few rare disorders do exist that are specific to deletions of genetic material or by mutations of specific genes on chromosome 17.

A type of leukemia known as acute promyelocytic leukemia is caused by the rearrangement of genetic material that is found on chromosome 17. Known as a translocation, the genetic material moves from chromosome 17 and attaches itself to an area on chromosome 15. This rearrangement creates a disruption on the normal regulation of the development of white blood cells. Before this rearrangement occurs, the genes are able to regulate and prevent abnormal white blood cell growth, thus preventing cancerous cells from forming. After this rearrangement, regulation is no longer possible and abnormal cell growth is allowed to continue which leads to the development of the leukemia. This specific type of translocation is rare and occurs in 1 out of 250,000 individuals. Diagnosis of this genetic disorder is usually made after the individual shows symptoms of this type of leukemia.

Smith-Magenis syndrome is a genetic disorder caused by a specific deletion of genetic material on chromosome 17. This syndrome is characterized by a number of physical, mental, and developmental abnormalities. Physical symptoms that are characteristic in the faces of individuals with this syndrome include deep set eyes, a broad and square shaped face, full and rosy cheeks, a broad lower jaw, and a down-turned mouth. Individuals often have low muscle tone, middle ear problems, a distinct walking gait, and a markedly decreased sensitivity to pain. Sleep disorders such as frequent waking through out the night and insomnia are also characteristic to this disorder. Although individuals are mentally delayed and will have delayed speech, their long-term memory for places, objects, and names is remarkable. Internal physical ailments include kidney problems, heart problems, and scoliosis. Most individuals afflicted with this disorder are extremely engaging and affectionate but will also have behavior problems due to attention deficit disorder, frequent temper tantrums, and aggression.

Miller-Dieker syndrome is another genetic disorder caused by a deletion of genetic material on chromosome 17. In this particular syndrome, the deletion causes the affected individual to have what is known as lissencephaly, or smooth brain. In normal cases, the brain has many folds and creases which give it its characteristic wrinkled appearance. Lissencephaly is caused by the lack of migration of the nerve cells during the end of the first trimester and the beginning of the second trimester of pregnancy. Failure of migration is a direct cause from the deletion of a specific gene known as LIS1. Other genes that have been found to be responsible for normal brain development are known as PAHAF1B1 and YWHAE. As with the LIS1 gene, these other genes are also deleted from chromosome 17 and are also not present in individuals with Miller-Dieker syndrome. While the smooth brain is the hallmark characteristic of Miller-Dieker syndrome, other symptoms include severe mental disabilities, developmental delays, seizures, and abnormal muscle formation that includes stiff muscles or weak muscle tone. Characteristic facial features include a wide forehead, a face that appears sunken in the middle, a small pixie-like upturned nose, low set ears, and a thick upper lip. Babies born with this condition have a difficult time feeding as they cannot swallow well and are prone to inhaling fluids into their lungs. Failure to thrive and pneumonia are common causes of death among infants with Miller-Dieker syndrome. Children who survive are slower to grow and may develop a small head (microcephaly). This disorder is rare and occurs in less than 1 out of every 100,000 live births.

17q21.31 microdeletion syndrome is caused by a very small deletion of a piece of chromosome 17. The q21.31 code designates the specific area of the chromosome where the deletion actually occurs. Individuals with this disorder have developmental delays that include mental disabilities and weak muscle tone. Physical characteristics of this syndrome include a broad and high forehead, upward pointing eyes that have narrow openings, a bulbous nose, and large ears. Many individuals have vision problems and males may also have undecended testicles. Some individuals may have congenital heart defects, kidney problems, skeletal deformities, and foot developmental abnormalities. This condition seems to be common in a small group of people who share a trait known as the H2 lineage. The H2 lineage is a variant of the 17q21.31 region found in 20% of the population of people of European and Middle Eastern decent but is rare in all other enthnicities. Those with the H2 lineage have a predisposition for the 17q21.31 region to break off from chromosome 17 or be deleted, giving rise to this syndrome in future generations. 17q21.31 microdeletion syndrome occurs in 1 out of 16,000 individuals although it often goes undiagnosed.

Like many other chromosomal disorders, there is no cure for the syndromes mentioned previously. Treatment is based on the individual’s condition and severity of symptoms. Mental disabilities can range from mild to severe depending on the type of chromosomal mutation. In the case of acute promyelocytic leukemia, individuals will need to be monitored by an oncologist as symptoms from this disorder can quickly become life-threatening.