TY - JOUR
T1 - Insufficient evidence for a role of SERPINF1 in otosclerosis
AU - Valgaeren, Hanne
AU - Sommen, Manou
AU - Beyens, Matthias
AU - Vandeweyer, Geert
AU - Schrauwen, Isabelle
AU - Schepers, Anne
AU - Schatteman, Isabelle
AU - Topsakal, Vedat
AU - Dhooge, Ingeborg
AU - Kunst, Henricus
AU - Zanetti, Diego
AU - Huber, Alexander M.
AU - Hoischen, Alexander
AU - Fransen, Erik
AU - Van Camp, Guy
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
KW - Otosclerosis
KW - Resequencing
KW - SERPINF1
KW - Single molecule-molecular inversion probes
UR - http://www.scopus.com/inward/record.url?scp=85069464137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069464137&partnerID=8YFLogxK
U2 - 10.1007/s00438-019-01558-8
DO - 10.1007/s00438-019-01558-8
M3 - Article
C2 - 30968248
AN - SCOPUS:85069464137
VL - 294
SP - 1001
EP - 1006
JO - Molecular Genetics and Genomics
JF - Molecular Genetics and Genomics
SN - 1617-4615
IS - 4
ER -