McLaughlin, Heather MKelly, Melissa AHawley, Pamela PDarras, BasilFunke, BirgitPicker, Jonathan2014-02-182013McLaughlin, Heather M, Melissa A Kelly, Pamela P Hawley, Basil T Darras, Birgit Funke, and Jonathan Picker. 2013. “Compound heterozygosity of predicted loss-of-function DES variants in a family with recessive desminopathy.” BMC Medical Genetics 14 (1): 68. doi:10.1186/1471-2350-14-68. http://dx.doi.org/10.1186/1471-2350-14-68.1471-2350http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717589Background: Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established. Case presentation: Next-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent. Conclusions: This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies.en-USDesminopathyMyopathyDilated cardiomyopathyClinical geneticsGenetic testingJournal Article2014-02-1810.1186/1471-2350-14-68