Chromosome 16
The 16p11.2 deletion syndrome is caused by a deletion of approximately 600,000 base pairs, (600 kb), at position 11.2 on the short arm (p) of chromosome 16. This deletion affects one of the two copies of the chromosome 16 in each cell The 600 kb region contains more than 25 genes, the elimination of which could be responsible for disorders such as intellectual disability; and autism spectrum disorder. Obesity is another common feature of 16p11.2 deletion syndrome; People with elimination also have an increased risk of seizures. Most people with elimination have some of these signs and symptoms, but others do not. Although some people have this elimination without serious consequences, they can still pass it on to their children, who may be more severely affected.
The 16p11.2 duplication presents an additional copy of the same 600 kb segment of chromosome 16 that is missing in the 16p11.2 deletion syndrome (described above). A doubling of 16p11.2 can result in signs and symptoms similar to elimination in some affected people, including the characteristics of autism spectrum disorder; However, being underweight is common in people with duplication, while obesity often occurs with elimination. 16p11.2 duplication seems to have a milder effect than elimination, with a greater proportion of individuals with this chromosomal change showing no apparent problems. These people can still transmit duplication to their children, who may have signs and symptoms related to chromosomal change.
A small amount of missing genetic material (520 kb) in the p arm of chromosome 16 causes a condition called 16p12.2 Microdelection, which is associated with physical and developmental abnormalities in some affected people. The deleted region contains seven genes. This removal affects one of two copies of chromosome 16 in each cell.
People have neurological or behavioral problems often have an additional and larger deletion or duplication that affects another chromosome. Small duplications of genetic material that occur near the 16p12.2 microdeletion may also contribute to the characteristics associated with this condition. Many people with missing genes in this region have no obvious signs or symptoms (a situation called incomplete penetrance), researchers believe that other genetic or environmental factors may also be involved.
Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD / MPV) is a disorder that affects the development of blood vessels in the lungs. It can be caused by a removal of genetic material on chromosome 16 in a region known as 16q24.1. This region includes several genes, including the FOXF1 gene. The FOXF1 protein helps regulate the development of the lungs and gastrointestinal tract. Genetic changes that result in a nonfunctional FOXF1 protein interfere with the development of pulmonary blood vessels and cause ACD / MPV. Affected babies may also have gastrointestinal abnormalities.
Cancer. Changes in the structure of chromosome 16 are associated with several types of cancer. These genetic changes are somatic, which means that they are acquired during a person's life. In some cases, chromosomal rearrangements called translocations interrupt the region of chromosome 16 that contains the CREBBP gene. Protein produced from this gene normally plays a role in the regulation of growth and cell division, which helps prevent the development of cancers. Researchers have found a translocation between chromosome 8 and chromosome 16 that disrupts the CREBBP gene in some people with a blood-forming cell cancer called Acute Myeloid Leukemia (AML). Another translocation has been found that involves the CREBBP gene, which reorganizes pieces of chromosomes 11 and 16, in some people who have received cancer treatment. This chromosomal change is associated with the subsequent development of AML and two other cancers of blood-forming tissues (chronic myeloid leukemia and myelodysplastic syndrome). These are sometimes described as treatment-related cancers because translocation between chromosomes 11 and 16 occurs after chemotherapy applied as a treatment for other types of cancer.
Acute myeloid leukemia (CBF-AML) is associated with rearrangements of genetic material on chromosome 16. The most common of these rearrangements is an inversion of a region of chromosome 16 (written as inv (16). An inversion involves the breakage of the chromosome in two places; the resulting DNA fragment is inverted and reinserted into the chromosome. Less frequently, a translocation occurs between the two copies of chromosome 16 (written as t (16; 16). Both types of genetic rearrangement result in the fusion of two genes found on chromosome 16, CBFB and MYH.11 These genetic changes are associated with 5 to 8% of cases of AML in adults.These mutations are acquired during the life of a person and are present only in certain cells.This type of genetic change, called somatic mutation, is not inherited.This anomaly causes an alteration of processes that involve several proteins (including DNA), and ultimately leads to production n of abnormal immature white blood cells called myeloid blasts and a shortage of normal mature blood cells. However, one or more additional genetic changes are needed for myeloid blasts to become cancerous leukemic cells.
Severe Rubinstein-Taybi syndrome (also known as chromosome 16p13.3 deletion syndrome); Some cases result from the removal of genetic material from the p arm of chromosome 16. When this deletion is present in all body cells, it can cause serious complications, such as the inability to gain weight and grow at the expected rate as well as a increased risk of life-threatening infections. Affected people also have many of the typical characteristics of Rubinstein-Taybi syndrome, which include intellectual disability, distinctive facial features and wide thumbs and first toes. Babies born with the severe form of this disorder usually survive until early childhood.
Other anomalies Trisomy 16 occurs when cells have three copies of chromosome 16 instead of the usual two copies. This condition causes serious health problems; Most affected infants die before or shortly after birth, although some have lived for weeks or months with intensive medical support. A similar but less severe condition called mosaic trisomy 16 occurs when only some of the body's cells have an extra copy of chromosome 16. The signs and symptoms of mosaic trisomy 16 vary widely and may include slow growth before birth ( intrauterine growth retardation), developmental delay and heart defects.
Other changes in the number or structure of chromosome 16 can have a variety of effects. Intellectual disability, stunted growth and development, distinctive facial features, weak muscle tone (hypotonia), heart defects and other medical problems are common. Frequent changes in chromosome 16 include an additional segment of the short (p) or long (q) arm of the chromosome in each cell (partial trisomy 16p or 16q) and a missing segment of the long arm of the chromosome in each cell (partial monosomy 16q ).
