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Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia.
- Source :
-
Journal of medical genetics [J Med Genet] 2020 Sep; Vol. 57 (9), pp. 643-646. Date of Electronic Publication: 2020 Mar 11. - Publication Year :
- 2020
-
Abstract
- Background: Mitochondrial progressive external ophthalmoplegia (PEO) encompasses a broad spectrum of clinical and genetic disorders. We describe the phenotypic subtypes of PEO and its correlation with molecular defects and propose a diagnostic algorithm.<br />Methods: Retrospective analysis of the clinical, pathological and genetic features of 89 cases.<br />Results: Three main phenotypes were found: 'pure PEO' (42%), consisting of isolated palpebral ptosis with ophthalmoparesis; Kearns-Sayre syndrome (10%); and 'PEO plus', which associates extraocular symptoms, distinguishing the following subtypes: : myopathic (33%), bulbar (12%) and others (3%). Muscle biopsy was the most accurate test, showing mitochondrial changes in 95%. Genetic diagnosis was achieved in 96% of the patients. Single large-scale mitochondrial DNA (mtDNA) deletion was the most frequent finding (63%), followed by multiple mtDNA deletions (26%) due to mutations in TWNK (n=8), POLG (n=7), TK2 (n=6) or RRM2B (n=2) genes, and point mtDNA mutations (7%). Three new likely pathogenic mutations were identified in the TWNK and MT-TN genes.<br />Conclusions: Phenotype-genotype correlations cannot be brought in mitochondrial PEO. Muscle biopsy should be the first step in the diagnostic flow of PEO when mitochondrial aetiology is suspected since it also enables the study of mtDNA rearrangements. If no mtDNA deletions are identified, whole mtDNA sequencing should be performed.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Adolescent
Biopsy
Child
Child, Preschool
DNA, Mitochondrial genetics
Female
Humans
Infant
Infant, Newborn
Kearns-Sayre Syndrome genetics
Kearns-Sayre Syndrome pathology
Male
Mitochondria pathology
Mitochondrial Diseases genetics
Mitochondrial Diseases pathology
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Ophthalmoplegia, Chronic Progressive External pathology
Phenotype
Point Mutation genetics
Thymidine Kinase
Cell Cycle Proteins genetics
DNA Helicases genetics
DNA Polymerase gamma genetics
Mitochondria genetics
Mitochondrial Proteins genetics
Ophthalmoplegia, Chronic Progressive External genetics
Ribonucleotide Reductases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1468-6244
- Volume :
- 57
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of medical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 32161153
- Full Text :
- https://doi.org/10.1136/jmedgenet-2019-106649