Rhabdomyolysis is a serious medical condition characterized by muscle injury, and there are recognized genetic causes especially in recurrent forms. The majority of these cases, however, remain unexplained. Here, we describe a patient with recurrent rhabdomyolysis in whom extensive clinical testing failed to identify a likely etiology. Whole-exome sequencing revealed a novel missense variant in MYH1, which encodes a major adult muscle fiber protein. Structural biology analysis revealed that the mutated residue is extremely well conserved and is located in the actin binding cleft. Furthermore, immediately adjacent mutations in that cleft in other myosins are pathogenic in humans. Our results are consistent with the finding that MYH1 is mutated in rhabdomyolysis in horses and suggest that this gene should be investigated in cases with recurrent rhabdomyolysis.
Bibliographical noteKAUST Repository Item: Exported on 2021-03-25
Acknowledged KAUST grant number(s): FCC/1/1976-25, REI/1/4446-01
Acknowledgements: We thank the study family for their enthusiastic participation. The research by Stefan T. Arold and Francisco J. Guzmán-Vega reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST) through the Award No. FCC/1/1976-25 and REI/1/4446-01 from the Office of Sponsored Research (OSR).
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