Evidence map›Paper›PMID 41053850›Full record

ArticleHuman genomics2025

A multicenter study reveals a novel pathogenic splice-site founder variant in OTOF.

Zippora Brownstein, Lara Kamal, Shir Mishan-Montefiori, Yael Hoffman, Dina Fine, Yoel Hirsch, Tzvi Weiden, Rivka Birnbaum, Hagar Mor-Shaked, Bella Davidov and 2 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Human genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Zippora Brownstein *Department of Human Molecular Genetics and Biochemistry, Gray Faculty of Medical and Health Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Lara Kamal *Department of Human Molecular Genetics and Biochemistry, Gray Faculty of Medical and Health Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Shir Mishan-MontefioriGenetic Institute, Barzilai Medical Center, Ashkelon, Israel.
Yael HoffmanThe Genetics Institute and Genomic Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Dina FineGenetic Institute, Kaplan Medical Center, Rehovot, Israel.
Yoel HirschDor Yeshorim, Committee for Prevention of Jewish Genetic Diseases, Brooklyn, NY, USA.
Tzvi WeidenDor Yeshorim, Committee for Prevention of Jewish Genetic Diseases, Jerusalem, Israel.
Rivka BirnbaumDepartment of Genetics, Hadassah Medical Center, Jerusalem, Israel.
Hagar Mor-ShakedDepartment of Genetics, Hadassah Medical Center, Jerusalem, Israel.
Bella DavidovRaphael Recanati Genetic Institute, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.
Yuval YaronThe Genetics Institute and Genomic Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Karen B AvrahamDepartment of Human Molecular Genetics and Biochemistry, Gray Faculty of Medical and Health Sciences and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. karena@tauex.tau.ac.il.

Funding

Breakthrough Award, Israel Science Foundation 2711/22Israel Science Foundation 3499/19
6 · The paper itself

Abstract

backgroundOver 200 pathogenic variants in the OTOF gene encoding otoferlin are associated with sensorineural hearing loss (SNHL) and auditory neuropathy spectrum disorders (ANSD).

resultsA novel splice variant, OTOF c.898-18G > A, was detected in seven Jewish Moroccan families with both SNHL and ANSD in an Israeli multicenter study. The effect on splicing was confirmed by a minigene assay, which demonstrated skipping of exon 10. This variant is absent in gnomAD and in all Jewish ethnic groups except for Moroccan Jews, with a carrier rate of 1.5% in this ancestry, suggesting a founder effect.

conclusionsThe OTOF variant represents a second founder allele associated with hearing loss in the Moroccan Jewish community and may serve as a candidate for gene therapy.

Indexed as

Founder EffectHearing Loss, CentralHearing Loss, SensorineuralMembrane ProteinsRNA Splice SitesExonsFemaleHumansIsraelJewsMaleMoroccoPedigreeMembrane ProteinsOTOF protein, humanRNA Splice SitesDeafnessGene therapyHearingOtoferlin

Identifiers

PMID41053850
PMCPMC12502505

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.