NSD1

The NSD1 gene provides instructions for making a protein whose exact function is unknown. This protein is active in many organs and tissues, including the brain, kidney, skeletal muscle, spleen, thymus (a small gland located behind the breastbone), and lung. Researchers believe that the NSD1 protein regulates the activity of certain genes involved in normal growth and development, and can turn genes on or off as needed.

Sotos syndrome - caused by mutations in the NSD1 gene

More than 100 mutations in the NSD1 gene have been identified in people with Sotos syndrome. The most common mutation in the Japanese population deletes genetic material from the region of chromosome 5 containing the NSD1 gene. In most other populations, mutations within the gene itself are more frequent. These mutations include insertions or deletions of a small amount of DNA and changes in single DNA building blocks (base pairs) that make up the gene. Most mutations prevent one copy of the NSD1 gene from making any protein or lead to the production of an abnormally small, nonfunctional version of the protein. It remains unclear how a reduced amount of the NSD1 protein during development leads to overgrowth, learning disabilities, and the other signs and symptoms of Sotos syndrome.

cancers - associated with the NSD1 gene

Changes in the activity of the NSD1 gene are associated with rare cases of a blood cancer called childhood acute myeloid leukemia. Gene activity is disrupted when part of chromosome 5 breaks off and reattaches to part of chromosome 11. This rearrangement of genetic material, called a translocation, abnormally fuses the NSD1 gene on chromosome 5 with the NUP98 gene on chromosome 11. Researchers are investigating how the fused NUP98-NSD1 gene is associated with the development of acute myeloid leukemia.

other disorders - associated with the NSD1 gene

Like Sotos syndrome, Weaver syndrome and Beckwith-Wiedemann syndrome are genetic conditions that involve overgrowth in childhood. Weaver syndrome is also characterized by a distinctive facial appearance, weak muscle tone (hypotonia) in infancy, joint problems, and a low-pitched cry. Typical signs and symptoms of Beckwith-Wiedemann syndrome include large body size, an enlarged tongue (macroglossia), ear and kidney abnormalities, and an increased risk of certain tumors. It remains controversial whether Weaver and Beckwith-Wiedemann syndromes can be caused by mutations in the NSD1 gene. A few studies have identified NSD1 mutations in rare cases of these disorders, but other researchers believe that these cases are more likely to be unusual presentations of Sotos syndrome.