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

BMC Medical Genetics

Jonathan Picker¹  Birgit Funke⁴  Basil T Darras³  Pamela P Hawley²  Melissa A Kelly⁵  Heather M McLaughlin⁵ 

[1] Department of Pediatrics, Harvard Medical School, Boston, MA, USA;Department of Pediatrics, Division of Genetics and Metabolism, Boston Children’s Hospital Boston, 300 Longwood Avenue, Division of Genetics, Hunnewell 5, Boston, MA, USA;Department of Neurology, Harvard Medical School, Boston, 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: Genetic testing;    Clinical genetics;    Dilated cardiomyopathy;    Myopathy;    Desminopathy;   

Others  :  1127709
DOI  :  10.1186/1471-2350-14-68

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

【 摘 要 】

Background

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.

【 授权许可】

   
2013 McLaughlin et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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