Disease relevance of MYH9

• Thus, our results suggest that mutations in MYH9 result in three megakaryocyte/platelet/leukocyte syndromes and are important in the pathogenesis of sensorineural deafness, cataracts and nephritis [1].
• Sequence analysis of MYH9 in a family with DFNA17 identified, at nucleotide 2114, a G-->A transposition that cosegregated with the inherited autosomal dominant hearing impairment [2].
• Moreover, it is demonstrated that MYH9 mutations also result in two other FTNS-like macrothrombocytopenia syndromes: Epstein syndrome (EPS) and Alport syndrome with macrothrombocytopenia (APSM) [3].
• Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma [4].
• Nonmuscle myosin heavy chain II-A is responsible for MYH9-related disease, which is characterized by macrothrombocytopenia, granulocyte inclusions, deafness, cataracts, and renal failure [5].

Psychiatry related information on MYH9

• MHA commited to mental health care [6].

High impact information on MYH9

• Among the identified candidate genes is the gene encoding nonmuscle myosin heavy chain 9 (MYH9; refs 8-10), which is expressed in platelets and upregulated during granulocyte differentiation [1].
• MHA and SBS can be differentiated by subtle ultrastructural leukocyte inclusion features, whereas FTNS is distinguished by the additional Alport-like clinical features of sensorineural deafness, cataracts and nephritis [1].
• May-Hegglin anomaly (MHA) is an autosomal dominant macrothrombocytopenia of unclear pathogenesis characterized by thrombocytopenia, giant platelets and leukocyte inclusions [7].
• The similarities between these platelet disorders and our recent refinement of the MHA (ref. 6) and FTNS (ref. 7) disease loci to an overlapping region of 480 kb on chromosome 22 suggested that all three disorders are allelic [1].
• Six- to 8 1/2-day inbred MHA/SsLak and outbred Syrian golden hamster embryos and 14-day fetal lungs, testes, and portions of small intestine were transplanted into cheek pouches or under kidney capsules of adult recipients [8].

Biological context of MYH9

• Haplotype analysis using three novel microsatellite markers revealed that three E1841K carriers--one with MHA and two with FTNS--shared a common haplotype around the MYH9 gene, suggesting a common ancestor [3].
• Our findings suggest that, at least for the Asp1424Asn mutation in the MYH9 gene, the phenotypes result from a highly unstable protein [9].
• The expression of MYH9 in the fetal and mature human kidney was studied, and the 40 coding exons of the gene were screened by single-strand conformation polymorphism in 12 families presenting with the association of MTCP and nephropathy [10].
• If further investigations confirm this latter result, the in vivo tyrosine phosphorylation of MYH9-ALK protein could involve mechanisms different from those described in the other ALK hybrid proteins [4].
• Nucleotide sequence of the MYH9-ALK chimeric cDNA revealed that the ALK breakpoint was different from all those previously reported [4].

Anatomical context of MYH9

• These 'MYH9-related' diseases are inherited as an autosomal dominant trait and are characterized by a variable expressivity of clinical features, including macrothrombocytopenia, deafness, nephrites, cataract, and Döhle-like leukocyte inclusions [11].
• Expression of MYH9 in the rat cochlea was confirmed using reverse transcriptase-PCR and immunohistochemistry [2].
• MYH9 was immunolocalized in the organ of Corti, the subcentral region of the spiral ligament, and the Reissner membrane [2].
• We hypothesize that haploinsufficiency of the MYH9 results in a failure to properly reorganize the cytoskeleton in megakaryocytes as required for efficient platelet production [9].
• We investigated the NMMHC-A localization in blood cells from eight MHA, SBS or FTNS patients with known MYH9 mutations [12].

Associations of MYH9 with chemical compounds

• The CK2 inhibitor 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole attenuated the phosphorylation of ACE and MYH9, disrupted their association, and enhanced the cleavage/secretion of ACE from the plasma membrane [13].
• The ACE-associated MYH9 immunoprecipitated from (32)P-labeled endothelial cells was basally phosphorylated and cell stimulation with ACE inhibitors, or with bradykinin, increased the phosphorylation of MYH9 [13].
• Many GPS platelets and some ES and MHA platelets were discoid and contained circumferential bundles of microtubules [14].
• Green fluorescent protein (GFP) was fused to the amino terminus of full-length human NMHC II-A, NMHC II-B, and delta N592 and the fusion proteins were stably expressed in HeLa cells by using a conditional expression system requiring absence of doxycycline [15].
• Signaling via the angiotensin-converting enzyme results in the phosphorylation of the nonmuscle myosin heavy chain IIA [13].

Physical interactions of MYH9

• These data indicate that menin through binding to NMHC II-A could participate in cell division and in other processes that involve NMHC II-A [16].

Enzymatic interactions of MYH9

• In this study, we found that nonmuscle myosin heavy chain-A (NMHC-A) is cleaved during apoptosis in Jurkat cells by using a cleavage-site-directed antibody for calpastatin [17].

Other interactions of MYH9

• Mutations in the non-muscle myosin heavy chain IIA gene (MYH9) are responsible for May-Hegglin anomaly, Sebastian, Fechtner and Epstein syndromes [11].
• The mRNAs encoding NMMHC-A and NMMHC-B are both 7.5 kb in size but are shown to be the products of different genes, which are localized to chromosome 22q11.2 and chromosome 17q13, respectively [18].
• Cutting edge: association of the motor protein nonmuscle myosin heavy chain-IIA with the C terminus of the chemokine receptor CXCR4 in T lymphocytes [19].
• MYH9 has never been associated with the development of acute leukemia, but MYH11 is disrupted in the M4 eosinophilia sub-type of AML (inv16) [20].
• MYH9 spectrum of autosomal-dominant giant platelet syndromes: unexpected association with fibulin-1 variant-D inactivation [21].

Analytical, diagnostic and therapeutic context of MYH9

• RESULTS: The results of denaturing high-performance liquid chromatography suggested a potential sequence alteration in exon 30 of MYH9 [22].
• Immunofluorescence analysis of neutrophil NMMHCA is useful as a screening test for the clear hematopathologic classification of MYH9 disorders [23].
• The approximately 54 kDa protein, possible breakdown product of MYH9, immunoreacted with MYH9 antibody in western blot analysis [24].
• Far-western blot analysis of MYH9 enriched by immunoprecipitation identified the native approximately 220 kDa protein as OGP-binding partner [24].
• Indirect immunofluorescence combining with PI nuclei staining technology is sensitive and more specific than Wright-Giemsa's staining in detecting MYH9-related disease inclusions, with which we might easily distinguish MYH9-related disease inclusions from infection-associated inclusions [25].

References