Evidence map›Paper›PMID 41033306›Full record

ArticleAmerican journal of human genetics2025

A cardiovascular, craniofacial, and neurodevelopmental disorder caused by loss-of-function variants in the eIF3 complex component genes EIF3A and EIF3B.

Esra Erkut, Cherith Somerville, Marci L B Schwartz, Laura McDonald, Qiliang Ding, Olivia M Moran, Xin Chen, Roozbeh Manshaei, Anne-Sophie Riedijk, Marie-Therese Schnürer and 41 more

Erratum issuedAbstract read
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In one paragraph

Article in American journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

51 authors.

Esra ErkutProgram in Developmental, Stem Cell & Cancer Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Cherith SomervilleTed Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada.
Marci L B SchwartzTed Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
Laura McDonaldProgram in Developmental, Stem Cell & Cancer Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Qiliang DingTed Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada.
Olivia M MoranTed Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
Xin ChenTed Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada.
Roozbeh ManshaeiTed Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada.
Anne-Sophie RiedijkProgram in Developmental, Stem Cell & Cancer Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Marie-Therese SchnürerProgram in Developmental, Stem Cell & Cancer Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Daniel C KoboldtThe Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, OH, USA.
Stylianos E AntonarakisMedigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland.
Emma C BedoukianChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Xavier BlancMedigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland.
Laura K ConlinChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Helen CoxBirmingham Women's and Children's Hospital, Birmingham, UK.
Karin E M DiderichDepartment of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands.
Bri DingmannSeattle Children's Hospital, University of Washington, Seattle, WA, USA.
Christèle DubourgService de Génétique Moléculaire et Génomique, CHU Pontchaillou, Rennes, France.
Frances ElmslieSt George's University Hospitals NHS Foundation Trust, London, UK.
Luis F EscobarMedical Genetics, Peyton Manning Children's Hospital, Ascension Health, Indianapolis, IN, USA.
Rachel GosselinDivision of Genetic and Genomic Medicine at Nationwide Children's Hospital, Columbus, OH, USA.
Maria J Guillen SacotoGeneDx LLC, Gaithersburg, MD, USA.
Cynthia D HaagMedical Genetics, Ascension St. Vincent, Indianapolis, IN, USA.
Lisa HerzigSeattle Children's Hospital, University of Washington, Seattle, WA, USA.
Ramanand JeeneeaBirmingham Women's and Children's Hospital, Birmingham, UK.
Priti KeniaBirmingham Women's and Children's NHS Trust, Birmingham, UK.
Konstantinos KolokotronisInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland.
Anna M KoppsGenetica AG, Zurich, Switzerland.
Christin KupperInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland.
Hayley LeesExeter Genomics Laboratory, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
Jacqueline LeonardChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Jonathan LevyGenetics Department, AP-HP, Robert Debré University Hospital, Paris, France.
Rebecca LittlejohnBaylor College of Medicine, Houston, TX, USA.
Demian MayerGenetica AG, Zurich, Switzerland.
Scott D McLeanBaylor College of Medicine, Houston, TX, USA.
Nikhil PattaniSt George's University Hospitals NHS Foundation Trust, London, UK.
Laurence PerrinGenetics Department, AP-HP, Robert Debré University Hospital, Paris, France.
Véronique PingaultService de Médecine Génomique des Maladies Rares, AP-HP, Hôpital Necker, Université Paris Cité, Paris, France.
Chloé QuelinService de Génétique Clinique, CLAD Ouest, CHU Rennes, Rennes, France.
Emmanuelle RanzaMedigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland.
Anita RauchInstitute of Medical Genetics, University of Zurich, Zurich, Switzerland.
Sara L ReichertChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Joana Rosmaninho-SalgadoMedical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Cara SkrabanChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
Sérgio SousaMedical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Melissa StuebbenBaylor College of Medicine, Houston, TX, USA.
Paolo ZanoniGenetica AG, Zurich, Switzerland; Luzerner Kantonsspital, Lucerne, Switzerland.
Raymond H KimTed Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Department of Medicine, University Health Network, Toronto, ON, Canada.
Ian C ScottProgram in Developmental, Stem Cell & Cancer Biology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. Electronic address: ian.scott@sickkids.ca.
Rebekah K JoblingTed Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Genome Diagnostics, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: rebekah.jobling@sickkids.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Syndromic cardiac malformations can result in morbidity, yet their genetic etiology is only understood for a subset of individuals. Genome sequencing efforts in congenital anomaly cohorts may identify disease-associated variants in previously unrecognized genes. Through international matchmaking efforts, we identified eighteen individuals in total with de novo or loss-of-function variants in EIF3A (n = 4) or EIF3B (n = 14). The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioral abnormalities. These genes encode core subunits of the eukaryotic initiation factor 3 (eIF3) complex, which plays a critical role in binding mRNA transcripts to the 40S ribosomal subunit during translation initiation. Both genes are highly constrained against loss of function, and animal models have demonstrated that disruptions in the eIF3 complex result in a range of developmental defects, including cardiovascular malformations. Additionally, EIF3B is located within the minimally overlapping region implicated in cardiac anomalies associated with 7p22.3 microdeletions. We sought to further study the role of these genes in syndromic congenital heart disease. To explore their functional impact, we generated zebrafish models with mutations in the orthologous eif3s10 and eif3ba genes, which resulted in developmental abnormalities, including thin heart tubes, lack of craniofacial cartilage, and embryonic lethality. We propose that pathogenic variants in EIF3A, as well as pathogenic variants or microdeletions involving EIF3B, cause a distinct autosomal-dominant neurodevelopmental syndrome characterized by cardiovascular and craniofacial manifestations.

Indexed as

Craniofacial AbnormalitiesEukaryotic Initiation Factor-3Heart Defects, CongenitalLoss of Function MutationNeurodevelopmental DisordersAnimalsChildChild, PreschoolFemaleHumansInfantMalePhenotypeZebrafishEIF3A protein, humanEukaryotic Initiation Factor-37p22.3 microdeletionscongenital heart diseasecraniofacialeIF3EIF3AEIF3Bneurodevelopmentalsyndromic CHDtetralogy of Fallotzebrafish models

Identifiers

PMID41033306
PMCPMC12808965

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