Label Name: MYH9 GENE1X
Lab Discipline: Molecular Diagnostics
Institution:  Duke University Health System 
EAP ID:  LAB6689 
Last Review:  3/27/2017 10:30:41 PM
Specimen Type
  Whole Blood (EDTA)
Container & Volume
  Age Group   Container   Volume  
  0  - 18 Years LAVENDER TOP TUBE 3  ML
Label Reminders
  Be sure to include patient's name, history #, date and time of collection, and collector's initials.
Collection Notes
  • Peripheral Blood: One lavender-top EDTA tube (minimum of 3 mls) is required for testing. Forward unprocessed peripheral blood promptly to the laboratory at ambient temperatures. THE SPECIMEN CANNOT BE FROZEN. GREEN-TOP (HEPARIN) TUBES ARE NOT ACCEPTABLE FOR TESTING.

    Amniocytes: 2-4ml of amniotic fluid is required. Forward promptly at ambient temperature only. Contact the Laboratory for additional information and instructions on sample requirements and shipping instructions. SPECIMEN CANNOT BE FROZEN.

    Cultured amniocytes / fibroblasts: Please contact the Laboratory for sample requirements and shipping instructions.

  Please deliver to lab at ambient temperature. If there is a delay of more than 24 hours in delivery, please refrigerate the sample. DO NOT FREEZE!
Turn Around Time -  Routine: 14-28 days   Stat: STAT is Unavailable
Reference Values
No mutation detected
  This assay uses PCR amplification followed by Sanger DNA sequencing to detect mutations in the MYH9 gene causative for MYH9-related disease. This assay only targets exons 1, 10, 16, 21, 24, 25, 26, 30, 31, 37, 38, 39, and 40 of the MYH9 gene. These specific coding sequences and flanking intronic sequences (minimum of 20 base pairs) are amplified from purified genomic DNA by PCR. The primers used for PCR contain M13 universal primer "tails" at their 5' ends, and have 3' ends that are homologous to their genomic target sequence. PCR products are treated with an exonuclease/phosphatase mixture (ExoSAP-IT) and sequenced using universal M13 forward and reverse primers (M13 Forward/-20 and M13 Reverse/-27) with the Big Dye Terminator v3.1 Cycle Sequencing Kit. These products are purified with the Big Dye XTerminator Purification Kit and resolved using the ABI 3130xl Genetic Analyzer. Data is analyzed by the ABI Data Collection software v3.0, Sequencing Analysis software 5.2 and SeqScape software v2.6.

This test was developed and its performance characteristics determined by the DUHS Clinical Molecular Diagnostics Laboratory. It has not been cleared or approved by the U.S. Food and Drug Administration. This test is used for clinical purposes. It should not be regarded as investigational or for research. This laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 ("CLIA") as qualified to perform high complexity clinical testing.
Special Information
  • Additional Patient Information Required: Due to the unique nature of genetic testing, patients offered this test should receive pre-test and post-test genetic counseling. Counseling should help the patient understand the strengths and limitations of DNA testing and the medical implications for the patient as well as for other family members. Patients are also required to give consent for testing.
Clinical Significance and Interpretive Data

The myosin heavy chain gene nine (MYH9, located on chromosome 22 (22q13.1)) encodes a nonmuscle myosin IIA heavy chain. MYH9 is a cytoskeletal contractile protein that plays a role in several important cellular functions, including cytokinesis, cell motility and maintenance of cell shape. MYH9 is expressed in the kidney, cochlea, and platelets and is upregulated during granulocytic differentiation. Mutations in MYH9 are associated with a spectrum of autosomal dominant macrothrombocytopenias with characteristic leukocyte inclusions (“Döhle-like” bodies), including May-Hegglin anomaly (MHA), Fechtner syndrome(FTNS) and Sebastian syndrome (SBS). FTNS is also characterized by nephritis, deafness, and cataracts. Other FTNS-like macrothrombocytopenias with MYH9 mutations include Epstein syndrome (EPS) and Alport syndrome with macrothrombocytopenia (APSM). The detection rate of MYH9 mutations for these five syndromes is aproximately 75% (20/27 patients in one study: Heath, K., et al. (2001)). Defects in MYH9 are also the cause of non-syndromic sensorineural deafness type 17 and macrothrombocytopenia with progressive sensorineural deafness. To date, 31 mutations of the MYH9 gene that cause macrothrombocytopenia have been identified. The prevalence of MYH9 gene mutations is low with only 106 families described in the literature. However, the presence of MYH9-gene-related disorders is probably underdiagnosed.

The cause of macrothrombocytopenias in patients with MHY9 mutations is related to the failure of reorganization of the megakaryocyte cytoskeleton during platelet production. Patients with these syndromes have a moderate bleeding tendency with menorrhagia and easy bruising being the most commonly reported symptoms. Additionally, polymorphisms in the MYH9 gene are associated with idiopathic and HIV-associated focal segmental glomerular sclerosis (FSGS), hypertensive end-stage renal disease, and albuminuria in hypertensive African-Americans.

Mutation analysis is important for disease diagnosis. In some cases in which the familial mutations are known, the analysis of one or two exons of the gene may be performed in lieu of full gene sequencing.


A definitive diagnosis of one of the syndromic forms of macrothrombocytopenia can be made through sequencing of the MYH9 gene and can aid physicians in distinguishing these macrothrombocytopenia syndromes from chronic idiopathic thrombocytopenic purpura (ITP) and other rare inherited platelet disorders, which would require a different therapeutic approach.

Precise knowledge of the disease causing mutations in an individual can aid in the genetic counseling of parents and family members. Because these diseases are most often inherited as autosomal dominant conditions, there is a 50% chance of transmission of the defective gene with each pregnancy. Additionally, siblings may be tested for the same mutation, and if present, would have a 50% chance of transmitting the defective gene to current or future children.


Coding and flanking intronic sequences are compared to a reference sequence. Sequence changes found in these regions will be reported as (1) known disease-causing mutations, (2) a mutation previously unreported, but of the type expected to cause the disease; i.e. frameshift mutations, nonsense mutations, etc. (3) sequence variation of uncertain clinical significance, or (4) benign polymorphisms. Variants of uncertain clinical significance may require additional studies including gene sequencing of other family members or other functional studies. All sequence changes, with the exception of benign polymorphisms, are confirmed by reamplification and resequencing of the relevant exon(s).


Althaus, K., and Greinacher, A. (2009) MYH9-related platelet disorders. Semin Thromb Hemost 35(2):189-203.

Freedman, B. et al. (2009) Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with albuminuria in hypertensive African Americans: the HyperGEN study. Am J Nephrology 29(6):626-32.

Freedman, B., et al. (2009) Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans. Kidney Int. 75(7):736-45.

Heath, K., et al. (2001) Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes. Am J Hum Genetics 69(5):1033-45.

Seri, M., et al. (2000) Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet 26(1):103-5.

    Patients with clinical symptoms consistent with any of the syndromes associated with macrothrombocytopenia sydnromes including May Hegglin anomaly, Fechtner syndrome and Sebastian syndrome and individuals with a family history of these syndromes may benefit from testing.
    Due to the rarity of MYH9-related diseases and the lack of comprehensive published MYH9 DNA mutation analysis data, the residual risk of having an MYH9 gene mutation that is not detected by the targeted gene sequencing approach used in this assay is unknown. These results are not intended to be used as the sole criteria for clinical diagnosis or patient management decisions and are not a substitute for a physician's judgment and clinical experience. Correlation with other laboratory testing or clinical findings is required.

The sensitivity and specificity of DNA sequencing is high for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed. Only select coding regions of the MYH9 gene and immediate flanking intronic sequences are examined (exons 1, 10, 16, 21, 24, 25, 26, 30, 31, 37, 38, 39, and 40). Changes in an exon not analyzed by this assay, farther into the introns, or in other non-coding regions of the gene would not be detected. Mutations in genes other than MYH9 would not be identified. Large deletions, duplications, multiple exon insertions, sequence alterations adversely affecting primer binding, and complete deletion of one allele may not be identified using these methods.
Test Synonyms
  Synonym(s): Alport Syndrome
Synonym(s): Epstein Syndrome
Synonym(s): Fechtner SYndrome
Synonym(s): Macrothrombocytopenia
Synonym(s): May-Hegglin Anomaly
Synonym(s): Myosin heavy polypeptide 9, non-muscle
Synonym(s): Sebastian Syndrome
Molecular Diagnostics Laboratory

Medical Director:
 Michael Datto, M.D., Ph.D.
 Phone: 919-684-6965
Lab Director:
 Catherine Rehder Ph.D, FACMG
 Phone: 919-613-8434
Lab Director:
 Siby Sebastian Ph.D., DABMG
 Phone: 919-613-8432

 Wadsworth Bldg, Cytogenetics, Rm 0220
 2351 Erwin Rd
 Durham,  NC  27705
 Phone: 919-684-2698
 FAX: 919-668-5424

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