Abstract
Mitochondrial diseases are multisystemic disorders characterized by an impairment of the mitochondrial respiratory chain. Diagnosis requires an approach that involves a high index of suspicion, molecular techniques and a careful selection of the tissue to be studied. Our goal was to develop and implement local strategies for diagnosing mitochondrial disorders, by standardizing procedures of molecular biology and nucleic acid sequencing. A prospective, analytical, observational study was conducted in a cohort of, a total of 82 patients with suspected mitochondrial disorder who were treated at our hospital between May 2008 and June 2019. We developed molecular diagnostic tools that included classical monogenic techniques and Next Generation Sequencing. We characterized the neurological and extra neurological manifestations noted in our cohort. Following the proposed algorithm, we obtained a molecular diagnostic performance of 54%, identifying mutations in 44 patients. mtDNA mutations were identified in 34 patients. Structural rearrangements in mitochondrial genome were found in 3 and 7 in nuclear genes, respectively. Our results confirm the utility of the proposed algorithm and the molecular tools used, as evidenced by a high diagnostic performance. This is of great value to a more efficient and comprehensive medical care of patients and families affected by mitochondrial disorders.
Highlights
Mitochondrial diseases are multisystemic disorders characterized by an impairment of the mitochondrial respiratory chain (RC)
Most of the proteins required for the correct functioning of mitochondria are encoded by nuclear genes, but 13 subunits of RC complexes are encoded by the mitochondrial genome [1]
The causal defect was found in 44 patients, obtaining in this way a diagnostic yield of 54% (Table 1)
Summary
Mitochondrial diseases are multisystemic disorders characterized by an impairment of the mitochondrial respiratory chain (RC). Most of the proteins required for the correct functioning of mitochondria are encoded by nuclear genes (nDNA), but 13 subunits of RC complexes are encoded by the mitochondrial genome (mtDNA) [1]. There are particular features of mtDNA that distinguish it from the nuclear genome: (a) each cell has hundreds to thousands of copies of mtDNA; (b) It is inherited only from the mother; (c) there could be a mixture of mtDNA populations in different proportions, where some harbor mutant alleles and some contain wild type sequences, a phenomenon called heteroplasmy [2]. Determining the level of heteroplasmy is important in mitochondrial disease diagnosis [3].
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