Genetic basis of mitochondrial diseases.
diagnostics
genetics
metabolic disorders
mitochondrial disease
multiomics
noncoding
oxidative phosphorylation
variants
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
17
02
2021
received:
25
01
2021
accepted:
18
02
2021
pubmed:
4
3
2021
medline:
21
7
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
Mitochondrial disorders are monogenic disorders characterized by a defect in oxidative phosphorylation and caused by pathogenic variants in one of over 340 different genes. The implementation of whole-exome sequencing has led to a revolution in their diagnosis, duplicated the number of associated disease genes, and significantly increased the diagnosed fraction. However, the genetic etiology of a substantial fraction of patients exhibiting mitochondrial disorders remains unknown, highlighting limitations in variant detection and interpretation, which calls for improved computational and DNA sequencing methods, as well as the addition of OMICS tools. More intriguingly, this also suggests that some pathogenic variants lie outside of the protein-coding genes and that the mechanisms beyond the Mendelian inheritance and the mtDNA are of relevance. This review covers the current status of the genetic basis of mitochondrial diseases, discusses current challenges and perspectives, and explores the contribution of factors beyond the protein-coding regions and monogenic inheritance in the expansion of the genetic spectrum of disease.
Identifiants
pubmed: 33655490
doi: 10.1002/1873-3468.14068
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1132-1158Informations de copyright
© 2021 Federation of European Biochemical Societies.
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