ArticleHuman molecular genetics2016
Mutations and altered expression of SERPINF1 in patients with familial otosclerosis.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Genome-wide screen of otosclerosis in population biobanks: 27 loci and shared associations with skeletal structure.Nature communications · 2023Pooled it
- Osteoprotegerin gene polymorphisms and otosclerosis: an additional genetic association study, multilocus interaction and meta-analysis.BMC medical genetics · 2020Pooled it
- Pigment Epithelium-Derived Factor Declines in Response to an Oral Glucose Load and Is Correlated with Vitamin D and BMI but Not Diabetes Status in Children and Young Adults.Hormone research in paediatrics · 2017Trial
- Heterozygous Nonsense Mutation in the Nuclear Transport FactorInternational journal of molecular sciences · 2026Article
- Exploring the genetic landscape of otosclerosis: current understanding and future perspectives.Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale · 2025Review
- Techniques for otosclerosis surgery: Ear surgery from the microscope to the endoscope - A literature review.Journal of otology · 2024Review
- Article
- Genetic variants and altered expression of SERPINF1 confer disease susceptibility in patients with otosclerosis.Journal of human genetics · 2023Article
- Unravelling the Impact of Cyclic Mechanical Stretch in Keratoconus-A Transcriptomic Profiling Study.International journal of molecular sciences · 2023Article
- Genetics of otosclerosis: finally catching up with other complex traits?Human genetics · 2022Review
- A wide range of protective and predisposing variants in aggrecan influence the susceptibility for otosclerosis.Human genetics · 2022Article
- A pathogenic deletion in Forkhead Box L1 (FOXL1) identifies the first otosclerosis (OTSC) gene.Human genetics · 2022Article
- Genetic Association of rs1021188 and DNA Methylation Signatures ofFrontiers in medicine · 2022Article
- The Acute Effects of Furosemide on Na-K-Cl Cotransporter-1, Fetuin-A and Pigment Epithelium-Derived Factor in the Guinea Pig Cochlea.Frontiers in molecular neuroscience · 2022Article
- Obesity alters the ovarian proteomic response to zearalenone exposure†.Biology of reproduction · 2021Article
- Article
- Identification of four hub genes as promising biomarkers to evaluate the prognosis of ovarian cancer in silico.Cancer cell international · 2020Article
- Insufficient evidence for a role of SERPINF1 in otosclerosis.Molecular genetics and genomics : MGG · 2019Article
- The CaBone · 2019Article
- Co-occurrence of heterozygous mutations inJournal of genetics · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Otosclerosis is a relatively common heterogenous condition, characterized by abnormal bone remodelling in the otic capsule leading to fixation of the stapedial footplate and an associated conductive hearing loss. Although familial linkage and candidate gene association studies have been performed in recent years, little progress has been made in identifying disease-causing genes. Here, we used whole-exome sequencing in four families exhibiting dominantly inherited otosclerosis to identify 23 candidate variants (reduced to 9 after segregation analysis) for further investigation in a secondary cohort of 84 familial cases. Multiple mutations were found in the SERPINF1 (Serpin Peptidase Inhibitor, Clade F) gene which encodes PEDF (pigment epithelium-derived factor), a potent inhibitor of angiogenesis and known regulator of bone density. Six rare heterozygous SERPINF1 variants were found in seven patients in our familial otosclerosis cohort; three are missense mutations predicted to be deleterious to protein function. The other three variants are all located in the 5'-untranslated region (UTR) of an alternative spliced transcript SERPINF1-012 RNA-seq analysis demonstrated that this is the major SERPINF1 transcript in human stapes bone. Analysis of stapes from two patients with the 5'-UTR mutations showed that they had reduced expression of SERPINF1-012 All three 5'-UTR mutations are predicted to occur within transcription factor binding sites and reporter gene assays confirmed that they affect gene expression levels. Furthermore, RT-qPCR analysis of stapes bone cDNA showed that SERPINF1-012 expression is reduced in otosclerosis patients with and without SERPINF1 mutations, suggesting that it may be a common pathogenic pathway in the disease.
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