MIR17HG

Genetic changes that reduce the amount of the MIR17HG gene cause Feingold syndrome type 2. This developmental disorder is characterized by abnormalities of the fingers and toes, particularly shortening of the second and fifth fingers (brachymesophalangy). Other common features include an unusually small head size (microcephaly) and learning disabilities. The mutations involved in this condition, known as 13q31.3 microdeletions, remove (delete) a small region of chromosome 13 that includes the MIR17HG gene and sometimes part or all of other nearby genes. Loss of the MIR17HG gene is thought to underlie the characteristic features of the disorder, although loss of other genes may play a role in some cases.

Deletion of one copy of the MIR17HG gene reduces the amount of miR-17~92 cluster miRNAs available to control the activity of specific genes during development before birth. While it is likely that the resulting disruption of signaling pathways leads to the problems with growth and development characteristic of Feingold syndrome type 2, it remains unclear exactly how a shortage of miR-17~92 cluster miRNAs causes the specific features of the condition.

Genetic changes, called microduplications, that result in an extra copy of the MIR17HG gene have been associated with developmental problems in a small number of people. Some individuals with these microduplications have overgrowth of the skeleton, resulting in extra fingers (polydactyly) and an unusually large head size (macrocephaly). Others with these microduplications have impaired growth, leading to short fingers (brachydactyly) and short stature. Affected individuals may also have features of autism spectrum disorder, which is characterized by impaired communication and social interaction. Researchers suggest that an extra copy of the MIR17HG gene disrupts normal skeletal growth, although they are unsure why the microduplications can either increase or reduce growth.

Genetic changes that result in extra copies of the MIR17HG gene have been found in cancer. These genetic changes likely occur when DNA makes a copy of itself (replicates) in preparation for cell division. Errors in the replication process can result in one or more extra copies of a gene within a cell, which is known as gene amplification. The amplifications are somatic, which means they are not inherited but instead occur in cells that give rise to the tumor. Gene amplifications involving MIR17HG have been found in a cancer of immune system cells called diffuse large B-cell lymphoma. Such amplifications are thought to increase the amount of miR-17~92 miRNAs. The resulting alterations to cell signaling pathways may lead to too much cell proliferation or too little apoptosis. As a result, cells can grow and divide uncontrollably, leading to the development of cancer.