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 CampEmail author
Original Article


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.


Otosclerosis SERPINF1 Single molecule-molecular inversion probes Resequencing 



We want to thank all participants of the study and Lie Cassiers, Marcel Cosgarea and Robert Vincent for their contribution.


This research was funded by the Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP) program (project IAP P7/43-BeMGI to G.V.C.). H.V. is supported by a PhD grant from the Flemish Agency for Innovation by Science and Technology (IWT, no. 131526). M.B. is supported by a PhD Grant from the Commissie Wetenschappelijk Onderzoek (CWO) from the University of Antwerp. G.V. is supported by the Research Foundation Flanders (FWO) (Grant no. 12D1717 N).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

438_2019_1558_MOESM1_ESM.docx (50 kb)
Supplementary material 1 (DOCX 49 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center of Medical GeneticsUniversity of Antwerp and Antwerp University HospitalAntwerpBelgium
  2. 2.Molecular and Human Genetics DepartmentCenter for Statistical Genetics, Baylor College of MedicineHoustonUSA
  3. 3.European Institute for ORL, St-Augustinus Hospital AntwerpAntwerpBelgium
  4. 4.Department of Otorhinolaryngology and Head and Neck SurgeryAntwerp University HospitalEdegemBelgium
  5. 5.Department of OtolaryngologyGhent University HospitalGhentBelgium
  6. 6.Department of Otorhinolaryngology, Hearing and GenesRadboud University Medical CenterNijmegenThe Netherlands
  7. 7.Department of Clinical Sciences and Community Health, Audiology UnitUniversity of Milan, I.R.C.C.S. Fondazione “Cà Granda”, Osp.le Maggiore PoliclinicoMilanItaly
  8. 8.Department of Otorhinolaryngology, Head and Neck SurgeryUniversity Hospital ZurichZurichSwitzerland
  9. 9.Department of Human Genetics, Radboud Institute for Molecular Life SciencesRadboud University Medical CenterNijmegenThe Netherlands
  10. 10.Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI)Radboud University Medical CenterNijmegenThe Netherlands
  11. 11.StatUa Center for StatisticsUniversity of AntwerpAntwerpBelgium

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