MYH9-specific laboratory technical considerations. MYH9 comprises 41 exons. The first exon does not code for amino acids; the first methionine of the open reading frame is in exon 2. Exon numbering may vary among different testing laboratories. Thrombocytopenia ranges from mild to severe. The degree of thrombocytopenia usually remains stable in each individual throughout life. Because platelet counts at the lower limit of the normal range have been reported in very few individuals with MYH9-RD, platelet macrocytosis and aggregates of the MYH9 protein in neutrophils are the only findings shared among all affected individuals. The diagnosis of MYH9-related disease is established in a proband with suggestive findings and a heterozygous pathogenic variant in MYH9 identified by molecular genetic testing (see Table 1).

A multigene panel that includes MYH9 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. If you are concerned about your family history and think your family may have MAP, consider asking the following questions:

Annually, or every 6 mos in genotypes w/high risk of kidney damage (See Genotype/Phenotype Correlations.)

Yes, if you would like to view MyHR guides, please visit : https://hr.qmul.ac.uk/myhr/myhrhowtoguides/ ASCO recommends the following screening for people with MAP. It is important to discuss these options with your health care team, as each individual is different: The story of H‑E‑B begins more than 100 years ago in a small, family‑owned store in the Texas Hill Country. Today, H‑E‑B serves families all over Texas and Mexico in 155 communities with more than 400 stores and over 120,000 employees. The need for prophylactic intervention in preparation for surgery or other invasive procedures (including platelet transfusion, short-term eltrombopag, and/or empiric use of antifibrinolytics drugs or desmopressin) should be established based on the type of procedure, the individual's previous history of bleeding, and platelet count before the procedure.

Platelet macrocytosis is present from birth in all individuals with MYH9-RD (see Diagnosis, Suggestive Findings). Options exist for people interested in having a child when a prospective parent may carry a genetic change that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic variant to reduce the likelihood that their children will inherit the condition. A person's eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parent(s) can then choose to transfer embryos which do not have the genetic variant. PGD has been in use for over 2 decades, and it has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic. How common is MAP? MYH9 encodes myosin-9, a protein of 1960 amino acids also known as the heavy chain of the non-muscle myosin IIA. Myosin-9 dimerizes and assembles with two essential and two regulatory light chains to constitute a hexameric molecule, the non-muscle myosin IIA (NMMIIA). NMMIIA assembles into functional bipolar filaments, which – interacting with actin – generate the mechanical force necessary for a variety of cellular processes, including motility and migration, cytokinesis, shape maintenance and change, and polarization. Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing and multigene panel) and comprehensive genomic testing ( exome sequencing and genome sequencing) depending on the phenotype.

Antifibrinolytic agents. Several authors recommend the systemic administration of antifibrinolytic agents, such as tranexamic or epsilon-aminocaproic acid, to treat mild or moderate mucocutaneous bleeding [ Althaus & Greinacher 2009]. Antifibrinolytic drugs are also used empirically as prophylaxis to cover surgery or other hemostatic challenges, especially low-risk procedures, in persons with MYH9-RD [ Orsini et al 2017]. Thrombocytopenia usually remains only disease manifestation throughout life 1 [ Pecci et al 2014a]. Specific cancer risks associated with MAP have not been determined. The risk of colorectal cancer is considered to be significantly increased, and there may be an increased risk of other cancers of the gastrointestinal tract and thyroid gland as well. What are the screening options for MAP?Sensorineural hearing loss is present in about 50% of individuals evaluated at a mean age of 33 years and is expected to occur in most individuals over time [ Pecci et al 2014a]. The mean age at onset is 31 years. Onset of hearing loss is distributed evenly from the first to sixth decade. Of those who develop hearing loss, 36% do so before age 20 years, 33% between ages 20 and 40 years, and 31% after age 40 years. For too many young British Muslims, the feeling of never quite belonging and having to meet conflicting social expectations, creates despair during the formative years of adolescence. In a community where most social issues are a cultural taboo, increasing numbers of young people are resorting to self-harm and substance abuse for escape, and mental health problems appear disproportionately higher. ​ Hearing loss interferes with activities of daily living in 90% of individuals who have an abnormal audiometric examination [ Pecci et al 2014a].