Encyclopedia
MYH9-related disorder is a condition that can have many signs and symptoms, including bleeding problems, hearing loss, kidney (renal) disease, and clouding of the lens of the eyes (cataracts).
- genetic conditions
Frequency
The incidence of MYH9-related disorder is unknown. More than 200 affected families have been reported in the scientific literature.
Causes
MYH9-related disorder is caused by mutations in the MYH9 gene. The MYH9 gene provides instructions for making a protein called myosin-9. This protein is one part (subunit) of the myosin IIA protein.
There are three forms of myosin II, called myosin IIA, myosin IIB and myosin IIC. The three forms are found throughout the body and perform similar functions. They play roles in cell movement (cell motility); maintenance of cell shape; and cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. While some cells use more than one type of myosin II, certain blood cells such as platelets and white blood cells (leukocytes) use only myosin IIA.
MYH9 gene mutations that cause MYH9-related disorder typically result in a nonfunctional version of the myosin-9 protein. The nonfunctional protein cannot properly interact with other subunits to form myosin IIA. Platelets and leukocytes, which only use myosin IIA, are most affected by a lack of functional myosin-9. It is thought that a lack of functional myosin IIA leads to the release of large, immature platelets in the bloodstream, resulting in a reduced amount of normal platelets. In leukocytes, the nonfunctional myosin-9 clumps together. These clumps of protein, called inclusion bodies, are a hallmark of MYH9-related disorder and are present in the leukocytes of everyone with this condition.
Inheritance
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
In most cases, an affected person inherits the mutation from one affected parent. Approximately 30 percent of cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
Other Names for This Condition
- autosomal dominant MYH9 spectrum disorders
- MYH9-related macrothrombocytopenias
- MYH9RD
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/myh9-related-disorder
References
- Althaus K, Greinacher A. MYH9-related platelet disorders. Semin Thromb Hemost.2009 Mar;35(2):189-203. doi: 10.1055/s-0029-1220327.
- Kunishima S, Saito H. Advances in the understanding of MYH9 disorders. CurrOpin Hematol. 2010 Sep;17(5):405-10. doi: 10.1097/MOH.0b013e32833c069c. Review.
- Savoia A, Pecci A. MYH9-Related Disorders. 2008 Nov 20 [updated 2015 Jul 16]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK2689/
- Sekine T, Konno M, Sasaki S, Moritani S, Miura T, Wong WS, Nishio H,Nishiguchi T, Ohuchi MY, Tsuchiya S, Matsuyama T, Kanegane H, Ida K, Miura K,Harita Y, Hattori M, Horita S, Igarashi T, Saito H, Kunishima S. Patients withEpstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressiveproteinuric renal disease. Kidney Int. 2010 Jul;78(2):207-14. doi:10.1038/ki.2010.21.
