G2Cdb::Allele report

Mutation type
P

Altered genes (1)

Gene Symbol Species Description
G00002004 MYH9 Homo sapiens myosin, heavy chain 9, non-muscle

Diseases (1)

Disease Description Nervous effect
D00000134 MYH9-related disease N

Literature (1)

Pubmed - human_disease

  • Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly.

    Franke JD, Dong F, Rickoll WL, Kelley MJ and Kiehart DP

    Department of Biology, Developmental Cell and Molecular Biology Group, Duke University Medical Center, Durham, NC 27708-1000, USA.

    MYH9-related disorders are autosomal dominant syndromes, variably affecting platelet formation, hearing, and kidney function, and result from mutations in the human nonmuscle myosin-IIA heavy chain gene. To understand the mechanisms by which mutations in the rod region disrupt nonmuscle myosin-IIA function, we examined the in vitro behavior of 4 common mutant forms of the rod (R1165C, D1424N, E1841K, and R1933Stop) compared with wild type. We used negative-stain electron microscopy to analyze paracrystal morphology, a model system for the assembly of individual myosin-II molecules into bipolar filaments. Wild-type tail fragments formed ordered paracrystal arrays, whereas mutants formed aberrant aggregates. In mixing experiments, the mutants act dominantly to interfere with the proper assembly of wild type. Using circular dichroism, we find that 2 mutants affect the alpha-helical coiled-coil structure of individual molecules, and 2 mutants disrupt the lateral associations among individual molecules necessary to form higher-order assemblies, helping explain the dominant effects of these mutants. These results demonstrate that the most common mutations in MYH9, lesions in the rod, cause defects in nonmuscle myosin-IIA assembly. Further, the application of these methods to biochemically characterize rod mutations could be extended to other myosins responsible for disease.

    Funded by: NHLBI NIH HHS: HL 66192; NIGMS NIH HHS: GM 33830

    Blood 2005;105;1;161-9

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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