Resolving complexity in mitochondrial disease: Towards precision medicine

Publication date: Available online 14 September 2019Source: Molecular Genetics and MetabolismAuthor(s): Róisín M. Boggan, Albert Lim, Robert W. Taylor, Robert McFarland, Sarah J. PickettAbstractMitochondrial diseases, caused by mutations in either the nuclear or mitochondrial genomes (mtDNA), are the most common form of inherited neurometabolic disorders. They are remarkably heterogeneous, both in their clinical presentation and genetic etiology, presenting challenges for diagnosis, clinical management and elucidation of molecular mechanism. The multifaceted nature of these diseases, compounded by the unique characteristics of mitochondrial genetics, cement their space in the field of complex disease. In this review we examine the m.3243A>G variant, one of the most prevalent mitochondrial DNA mutations, using it as an exemplar to demonstrate the challenges presented by these complex disorders. Disease caused by m.3243A>G is one of the most phenotypically diverse of all mitochondrial diseases; we outline known causes of this heterogeneity including mtDNA heteroplasmy, mtDNA copy number and nuclear genetic factors. We consider the impact that this has in the clinic, discussing the personalized management of common manifestations attributed to this pathogenic mtDNA variant, including hearing impairment, diabetes mellitus, myopathy, cardiac disease, stroke-like episodes and gastrointestinal disturbances. Future research into this complex disorder must account ...
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research

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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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