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

Johanna Elander, Elizabeth M McCormick, Maria Värendh, Karin Stenfeldt, Rebecca D Ganetzky, Amy Goldstein, Zarazuela Zolkipli-Cunningham, Laura E MacMullen, Rui Xiao, Marni J Falk, Johannes K Ehinger

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)230-238
Antal sidor9
TidskriftMolecular Genetics and Metabolism
Volym137
Nummer3
DOI
StatusPublished - 2022 nov.

Bibliografisk information

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Ämnesklassifikation (UKÄ)

  • Oto-rino-laryngologi
  • Medicinsk genetik

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