Insufficient evidence for a role of SERPINF1 in otosclerosis

Hanne Valgaeren, Manou Sommen, Matthias Beyens, Geert Vandeweyer, Isabelle Schrauwen, Anne Schepers, Isabelle Schatteman, Vedat Topsakal, Ingeborg Dhooge, Henricus Kunst, Diego Zanetti, Alexander M. Huber, Alexander Hoischen, Erik Fransen, Guy Van Camp

Research output: Contribution to journalArticlepeer-review


Otosclerosis is a common form of hearing loss (HL) due to abnormal remodeling of the otic capsule. The genetic causes of otosclerosis remain largely unidentified. Only mutations in a single gene, SERPINF1, were previously published in patients with familial otosclerosis. To unravel the contribution of genetic variation in this gene to otosclerosis, this gene was re-sequenced in a large population of otosclerosis patients and controls. Resequencing of the 5′ and 3′ UTRs, coding regions, and exon–intron boundaries of SERPINF1 was performed in 1604 unrelated otosclerosis patients and 1538 unscreened controls, and in 62 large otosclerosis families. Our study showed no enrichment of rare variants, stratified by type, in SERPINF1 in patients versus controls. Furthermore, the c.392C > A (p.Ala131Asp) variant, previously reported as pathogenic, was identified in three patients and four controls, not replicating its pathogenic nature. We could also not find evidence for a pathogenic role in otosclerosis for 5′ UTR variants in the SERPINF1-012 transcript (ENST00000573763), described as the major transcript in human stapes. Furthermore, no rare variants were identified in the otosclerosis families. This study does not support a pathogenic role for variants in SERPINF1 as a cause of otosclerosis. Therefore, the etiology of the disease remains largely unknown and will undoubtedly be the focus of future studies.

Original languageEnglish
Pages (from-to)1001-1006
Number of pages6
JournalMolecular Genetics and Genomics
Issue number4
Publication statusPublished - Aug 1 2019


  • Otosclerosis
  • Resequencing
  • Single molecule-molecular inversion probes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics


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