ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Variants affecting diverse domains of MEPE are associated with two distinct bone disorders, a craniofacial bone defect and otosclerosis.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 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
- Knockdown of MEPE Promotes Cranial Defect Repair and Activates the cAMP/PKA Signaling Pathway.Biochemical genetics · 2026Article
- 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
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- Article
- Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.International journal of molecular sciences · 2023Article
- Targeted Resequencing of Otosclerosis Patients from Different Populations Replicates Results from a Previous Genome-Wide Association Study.Journal of clinical medicine · 2022Article
- 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
- Genetic Association of rs1021188 and DNA Methylation Signatures ofFrontiers in medicine · 2022Article
- FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.International journal of molecular sciences · 2021Review
- Insufficient evidence for a role of SERPINF1 in otosclerosis.Molecular genetics and genomics : MGG · 2019Article
- The CaBone · 2019Article
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Authors and funding
31 authors at 10 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP) family and otosclerosis.
methodsWe performed exome sequencing in a four-generation family presenting nonprogressive HCFP and mixed hearing loss (HL). MEPE was analyzed using either Sanger sequencing or molecular inversion probes combined with massive parallel sequencing in 89 otosclerosis families, 1604 unrelated affected subjects, and 1538 unscreened controls.
resultsExome sequencing in the HCFP family led to the identification of a rare segregating heterozygous frameshift variant p.(Gln425Lysfs*38) in MEPE. As the HL phenotype in this family resembled otosclerosis, we performed variant burden and variance components analyses in a large otosclerosis cohort and demonstrated that nonsense and frameshift MEPE variants were significantly enriched in affected subjects (p = 0.0006-0.0060).
conclusionMEPE exerts its function in bone homeostasis by two domains, an RGD and an acidic serine aspartate-rich MEPE-associated (ASARM) motif inhibiting respectively bone resorption and mineralization. All variants associated with otosclerosis are predicted to result in nonsense mediated decay or an ASARM-and-RGD-truncated MEPE. The HCFP variant is predicted to produce an ASARM-truncated MEPE with an intact RGD motif. This difference in effect on the protein corresponds with the presumed pathophysiology of both diseases, and provides a plausible molecular explanation for the distinct phenotypic outcome.
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