Compound heterozygosity of predicted loss-of-function DESvariants in a family with recessive desminopathy

BMC Medical Genetics

Case Report

Pamela P Hawley¹  Jonathan Picker²  Basil T Darras³  Heather M McLaughlin⁴  Birgit Funke⁵  Melissa A Kelly⁶ 

[1] Department of Pediatrics, Division of Genetics and Metabolism, Division of Genetics, Boston Children’s Hospital Boston, 300 Longwood Avenue, Hunnewell 5, Boston, MA, USA;Department of Pediatrics, Division of Genetics and Metabolism, Division of Genetics, Boston Children’s Hospital Boston, 300 Longwood Avenue, Hunnewell 5, Boston, MA, USA;Department of Pediatrics, Harvard Medical School, Boston, MA, USA;Division of Clinical Neurology, Children’s Hospital Boston, Boston, MA, USA;Department of Neurology, Harvard Medical School, Boston, MA, USA;Laboratory for Molecular Medicine, 65 Landsdowne Street, 02139, Cambridge, MA, USA;Laboratory for Molecular Medicine, Partners Center for Personalized Genetic Medicine, 65 Lansdowne St. Cambridge, Cambridge, MA, USA;Laboratory for Molecular Medicine, 65 Landsdowne Street, 02139, Cambridge, MA, USA;Laboratory for Molecular Medicine, Partners Center for Personalized Genetic Medicine, 65 Lansdowne St. Cambridge, Cambridge, MA, USA;Department of Pathology, Massachusetts General Hospital, Boston, MA, USA;Laboratory for Molecular Medicine, Partners Center for Personalized Genetic Medicine, 65 Lansdowne St. Cambridge, Cambridge, MA, USA;

关键词: Desminopathy;    Myopathy;    Dilated cardiomyopathy;    Clinical genetics;    Genetic testing;   

DOI  :  10.1186/1471-2350-14-68

 received in 2012-12-22, accepted in 2013-06-24,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundVariants 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 presentationNext-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.ConclusionsThis 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.

【 授权许可】

Unknown   
© McLaughlin et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.