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Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease

Elander, Johanna LU ; McCormick, Elizabeth M ; Värendh, Maria LU ; Stenfeldt, Karin LU orcid ; Ganetzky, Rebecca D ; Goldstein, Amy ; Zolkipli-Cunningham, Zarazuela ; MacMullen, Laura E ; Xiao, Rui and Falk, Marni J , et al. (2022) In Molecular Genetics and Metabolism 137(3). p.230-238
Abstract

In this retrospective cohort study of 193 consecutive subjects with primary mitochondrial disease (PMD) seen at the Children's Hospital of Philadelphia Mitochondrial Medicine Frontier Program, we assessed prevalence, severity, and time of onset of sensorineural hearing loss (SNHL) for PMD cases with different genetic etiologies. Subjects were grouped by genetic diagnosis: mitochondrial DNA (mtDNA) pathogenic variants, single large-scale mtDNA deletions (SLSMD), or nuclear DNA (nDNA) pathogenic variants. SNHL was audiometrically confirmed in 27% of PMD subjects (20% in mtDNA pathogenic variants, 58% in SLSMD and 25% in nDNA pathogenic variants). SLSMD had the highest odds ratio for SNHL. SNHL onset was post-lingual in 79% of PMD cases,... (More)

In this retrospective cohort study of 193 consecutive subjects with primary mitochondrial disease (PMD) seen at the Children's Hospital of Philadelphia Mitochondrial Medicine Frontier Program, we assessed prevalence, severity, and time of onset of sensorineural hearing loss (SNHL) for PMD cases with different genetic etiologies. Subjects were grouped by genetic diagnosis: mitochondrial DNA (mtDNA) pathogenic variants, single large-scale mtDNA deletions (SLSMD), or nuclear DNA (nDNA) pathogenic variants. SNHL was audiometrically confirmed in 27% of PMD subjects (20% in mtDNA pathogenic variants, 58% in SLSMD and 25% in nDNA pathogenic variants). SLSMD had the highest odds ratio for SNHL. SNHL onset was post-lingual in 79% of PMD cases, interestingly including all cases with mtDNA pathogenic variants and SLSMD, which was significantly different from PMD cases caused by nDNA pathogenic variants. SNHL onset during school age was predominant in this patient population. Regular audiologic assessment is important for PMD patients, and PMD of mtDNA etiology should be considered as a differential diagnosis in pediatric patients and young adults with post-lingual SNHL onset, particularly in the setting of multi-system clinical involvement. Pathogenic mtDNA variants and SLSMD are less likely etiologies in subjects with congenital, pre-lingual onset SNHL.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Young Adult, Humans, Child, DNA, Mitochondrial/genetics, Retrospective Studies, Mitochondrial Diseases/complications, Hearing Loss, Sensorineural/genetics, Mitochondria/genetics
in
Molecular Genetics and Metabolism
volume
137
issue
3
pages
9 pages
publisher
Elsevier
external identifiers
  • scopus:85139057258
  • pmid:36182714
ISSN
1096-7192
DOI
10.1016/j.ymgme.2022.09.002
project
Mitochondrial reasons for hearing loss
language
English
LU publication?
yes
additional info
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
id
bbdb4349-d3af-4390-ae08-f71682d49af7
date added to LUP
2022-11-28 13:27:53
date last changed
2024-04-18 07:46:28
@article{bbdb4349-d3af-4390-ae08-f71682d49af7,
  abstract     = {{<p>In this retrospective cohort study of 193 consecutive subjects with primary mitochondrial disease (PMD) seen at the Children's Hospital of Philadelphia Mitochondrial Medicine Frontier Program, we assessed prevalence, severity, and time of onset of sensorineural hearing loss (SNHL) for PMD cases with different genetic etiologies. Subjects were grouped by genetic diagnosis: mitochondrial DNA (mtDNA) pathogenic variants, single large-scale mtDNA deletions (SLSMD), or nuclear DNA (nDNA) pathogenic variants. SNHL was audiometrically confirmed in 27% of PMD subjects (20% in mtDNA pathogenic variants, 58% in SLSMD and 25% in nDNA pathogenic variants). SLSMD had the highest odds ratio for SNHL. SNHL onset was post-lingual in 79% of PMD cases, interestingly including all cases with mtDNA pathogenic variants and SLSMD, which was significantly different from PMD cases caused by nDNA pathogenic variants. SNHL onset during school age was predominant in this patient population. Regular audiologic assessment is important for PMD patients, and PMD of mtDNA etiology should be considered as a differential diagnosis in pediatric patients and young adults with post-lingual SNHL onset, particularly in the setting of multi-system clinical involvement. Pathogenic mtDNA variants and SLSMD are less likely etiologies in subjects with congenital, pre-lingual onset SNHL.</p>}},
  author       = {{Elander, Johanna and McCormick, Elizabeth M and Värendh, Maria and Stenfeldt, Karin and Ganetzky, Rebecca D and Goldstein, Amy and Zolkipli-Cunningham, Zarazuela and MacMullen, Laura E and Xiao, Rui and Falk, Marni J and Ehinger, Johannes K}},
  issn         = {{1096-7192}},
  keywords     = {{Young Adult; Humans; Child; DNA, Mitochondrial/genetics; Retrospective Studies; Mitochondrial Diseases/complications; Hearing Loss, Sensorineural/genetics; Mitochondria/genetics}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{230--238}},
  publisher    = {{Elsevier}},
  series       = {{Molecular Genetics and Metabolism}},
  title        = {{Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease}},
  url          = {{http://dx.doi.org/10.1016/j.ymgme.2022.09.002}},
  doi          = {{10.1016/j.ymgme.2022.09.002}},
  volume       = {{137}},
  year         = {{2022}},
}