Lopriore, Piervito and Legati, Andrea and Neuhofer, Christiane Michaela and Lo Gerfo, Annalisa and Kopajtich, Robert and Barresi, Marco and Cecchi, Giulia and Pavlov, Martin and Izzo, Rossella and Montano, Vincenzo and Caligo, Maria Adelaide and Berutti, Riccardo and Mancuso, Michelangelo and Prokisch, Holger and Ghezzi, Daniele (2025) An inherited mtDNA rearrangement, mimicking a single large-scale deletion, associated with MIDD and a primary cardiological phenotype. MITOCHONDRION, 83: 102037. ISSN 1567-7249, 1872-8278
Full text not available from this repository. (Request a copy)Abstract
Aim: To identify the genetic cause in a previously unsolved pedigree, with mother and two daughters suffering of dilated cardiomyopathy with prevailing arrhythmic burden associated with diabetes mellitus and sensorineural hearing loss, without clear evidence of progressive external ophthalmoplegia. Methods: Several genetic tests were performed over the years including single-gene sequencing, mitochondrial DNA (mtDNA) sequencing, NGS panel for mitochondrial diseases and cardiomyopathies, clinical exome sequencing and whole exome sequencing. Specific amplifications and long-read NGS were used to evaluate mtDNA structural alterations. Results: By means of whole exome sequencing we found a novel heteroplasmic 12 kb-long single deletion in the mtDNA in all affected family members, confirmed by long-range PCR. However, a deeper investigation by long-read NGS revealed indeed the presence of rearranged mtDNA species, formed by a wild-type plus a deleted molecule. This mtDNA duplication turned out to be inherited in our pedigree and present in all tested specimens. Conclusion: While mtDNA single large-scale deletions are generally considered sporadic, few old reports described maternally inherited mtDNA duplication We suggest that mtDNA large rearrangements should be considered as possible disease causes in familial cases with unusual mitochondrial phenotypes. Long-read sequencing is useful for the detection of these variants, particularly mtDNA duplications.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MITOCHONDRIAL-DNA DELETION; CARDIOMYOPATHY; Mitochondrial DNA; mtDNA; Structural rearrangement; mtDNA duplication; Single large-scale deletion; MIDD (Maternally Inherited Diabetes and Deafness) |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2026 06:35 |
| Last Modified: | 20 Apr 2026 06:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67637 |
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