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Lopriore, P.* ; Legati, A.* ; Neuhofer, C. ; Gerfo, A.L.* ; Kopajtich, R. ; Barresi, M.* ; Cecchi, G.* ; Pavlov, M. ; Izzo, R.* ; Montano, V.* ; Caligo, M.A.* ; Berutti, R. ; Mancuso, M.* ; Prokisch, H. ; Ghezzi, D.*

An inherited mtDNA rearrangement, mimicking a single large-scale deletion, associated with MIDD and a primary cardiological phenotype.

Mitochondrion 83:102037 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mitochondrial Dna ; Single Large-scale Deletion ; Structural Rearrangement ; Mtdna ; Mtdna Duplication; Mitochondrial-dna Deletion; Cardiomyopathy
ISSN (print) / ISBN 1567-7249
e-ISSN 1872-8278
Zeitschrift Mitochondrion
Quellenangaben Band: 83, Heft: , Seiten: , Artikelnummer: 102037 Supplement: ,
Verlag Elsevier
Verlagsort 125 London Wall, London, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen European Union - Next Generation EU
Italian Ministry of Health
EJPRD project GENOMIT