This report describes MYH9-related disorder, an autosomal dominant disorder caused by dysfunction of one of the human non-muscle myosin heavy chain genes, myosin heavy chain 9. In OMIM, this disease is designated 'macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss' (MATINS). In Drosophila, there is a single non-muscle myosin II heavy chain gene, zip, to which MYH9 is closely related. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\zip. This fly gene is also orthologous to three other non-muscle myosin II heavy chain genes in human, MYH10, MYH11, and MYH14.
A UAS construct of a wild-type human Hsap\MYH9 gene has been introduced into flies, but has not been characterized.
Variant(s) implicated in human disease tested (as analogous mutation in fly gene): N98K in the fly zip gene (corresponds to N93K in the human MYH9 gene); R707C in the fly zip gene (corresponds to R702C in the human MYH9 gene); R1171C in the fly zip gene (corresponds to R1165C in the human MYH9 gene); D1430N in the fly zip gene (corresponds to D1424N in the human MYH9 gene); D1847K in the fly zip gene (corresponds to E1841K in the human MYH9 gene), R1939* in the fly zip gene (corresponds to R1933* in the human MYH9 gene).
Disease-related variant forms of Dmel\zip exhibit dominant phenotypes only when placed in particular genetic backgrounds. In a study directed specifically to the role of Dmel\zip in auditory organs, over-expression of 4 disease-related variant forms of zip in Johnston's organ results in scolopidial detachment (with variable penetrance); subcellular localization of the zip variant myosins was also affected. Ubiquitination as a regulator of myosin function has been investigated in the fly disease model system.
In flies, most mutations of zip exhibit recessive phenotypes. Animals homozygous for an amorphic mutation exhibit multiple defects during embryogenesis, most prominently, incomplete dorsal closure. Extensive physical and genetic interactions have been described for Dmel\zip; see below and in the zip gene report.
[updated January 2020 by FlyBase; FBrf0222196]
[MACROTHROMBOCYTOPENIA AND GRANULOCYTE INCLUSIONS WITH OR WITHOUT NEPHRITIS OR SENSORINEURAL HEARING LOSS; MATINS](https://omim.org/entry/155100)
[MYOSIN, HEAVY CHAIN 9, NONMUSCLE; MYH9](https://omim.org/entry/160775)
MYH9-related disorder (MYH9RD) is characterized by large platelets and thrombocytopenia, both of which are present from birth. MYH9RD is variably associated with progressive sensorineural hearing loss, which may be present from birth or can develop anytime into late adulthood; it is also variably associated with renal disease and cataracts. MYH9RD was previously classified as multiple different disorders (Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, or Sebastian syndrome), dependent upon different combinations of clinical findings. [from Medgene, MYH9 related disorders; 2017.12.02]
Originally described as multiple different syndromes with overlapping symptoms: Epstein syndrome (MIM:153650), Fechtner syndrome (MIM:153640), May-Hegglin anomaly (MIM:155100), Sebastian syndrome (MIM:605249). Two additional diseases, a sub-type of non-syndromic autosomal dominant deafness (MIM:603622) and Macrothrombocytopenia and progressive sensorineural deafness (MIM:600208) are also associated with MYH9. [from MIM:160775; 2017.12.04]
Causative gene is MYH9; exhibits autosomal dominant inheritance. [from Medgene, MYH9 related disorders; 2017.12.02]
MYH9 (myosin, heavy chain 9, nonmuscle) encodes a nonmuscle myosin heavy chain expressed in fibroblasts, endothelial cells, and macrophages. [from MIM:160775; 2017.12.04]
Many to one: 4 human to 1 Drosophila; the human genes are MYH9, MYH10, MYH11, and MYH14.
Moderate- to high-scoring ortholog of human genes MYH9, MYH10, MYH11, and MYH14 (1 Drosophila to 4 human). Dmel\zip shares 56-61% identity and 73-77% similarity with the human genes.
