Proteinuria

Gene: MYH9

Green List (high evidence)

MYH9 (myosin heavy chain 9)
EnsemblGeneIds (GRCh38): ENSG00000100345
EnsemblGeneIds (GRCh37): ENSG00000100345
OMIM: 160775, Gene2Phenotype
MYH9 is in 12 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

MYH9-Related Disorders are a class of autosomal dominant disorders characterised by congenital macrothrombocytopenia and variable leucocyte inclusion bodies, renal abnormalities, cataracts, and progressive sensorineural hearing loss.

Missense variants are located at only 21 of the 1,960 amino acid residues of the protein, and nonsense or frameshift variants have only been reported in the last exon of the gene. There are several reports of the p.Arg705His variant in MYH9 causing nonsyndromic hearing loss, DFNA17 (Lalwani 2000, Hildebrand 2006). However, no testing for the blood phenotype was reported in any affected individuals in these families, and at least two other individuals with the hematological features of MYH9-RD had the same variant (Verver 2015). These data suggest nonsyndromic hearing loss may not be a distinct entity from MYH9-RD. Hearing loss is not a fully penetrant feature of MYH9-RD; a review of cases indicated approximately 48% of patients have hearing loss (Pecci 2014). Individuals presenting with nonsyndromic hearing loss who are found to have a pathogenic variant in MYH9 should be tested for the other phenotypes of MYH9-RD.

In vitro functional evidence indicates that disease-causing variants may act through different molecular mechanisms in different cell types (Franke 2005, Hu 2002, Pecci 2005), exhibiting a dominant-negative effect on wild-type protein in granulocytes and haploinsufficiency in megakaryocytes and platelets (Pecci 2005). Four knock-in mouse models harboring 3 different human variants in MYH9 fully recapitulated the human phenotype of MYH9-RD (Zhang 2012, Suzuki 2013).

DEFINITIVE by ClinGen for the broader MYH9-related disorders.
Created: 30 Sep 2020, 11 p.m. | Last Modified: 30 Sep 2020, 11 p.m.
Panel Version: 0.4690

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Deafness, autosomal dominant 17, MIM# 603622; Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, MIM# 155100; MYH9-related disorders

Publications

Details

Mode of Inheritance
Unknown
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
  • Victorian Clinical Genetics Services
  • Expert Review Green
OMIM
160775
Clinvar variants
Variants in MYH9
Penetrance
None
Panels with this gene

History Filter Activity

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: MYH9 was added gene: MYH9 was added to Nephrotic Syndrome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: MYH9 was set to Unknown