Evidence map›Paper›PMID 32413283›Full record

ArticleAmerican journal of human genetics2020

Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling.

Thuy-Linh Le, Yunia Sribudiani, Xiaomin Dong, Céline Huber, Chelsea Kois, Geneviève Baujat, Christopher T Gordon, Valerie Mayne, Louise Galmiche, Valérie Serre and 22 more

Open access · bronzeAbstract read
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In one paragraph

Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
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

19 citing papers in PubMed, 33 citations in OpenAlex.

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  5. A Novel Variant in the Cyto-Tail ofMolecular syndromology · 2024
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  6. Clinical and molecular heterogeneity of syndromic hypothalamic hamartoma.American journal of medical genetics. Part A · 2023
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  7. Article
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  9. Review
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  15. Article
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  17. Article
  18. Atrial and Sinoatrial Node Development in the Zebrafish Heart.Journal of cardiovascular development and disease · 2021
    Review
  19. Review
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

32 authors at 11 institutions in 5 countries.

Thuy-Linh LeUniversité de Paris, Imagine Institute, Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, 75015 Paris, France.
Yunia SribudianiDepartment of Clinical Genetics, Erasmus Medical Center, 3015 GD Rotterdam, the Netherlands; Department of Biomedical Sciences, Division of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Padjadjaran, Bandung 40132, Indonesia.
Xiaomin DongBrain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, 3010 Victoria, Australia.
Céline HuberUniversité de Paris, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, 75015 Paris, France.
Chelsea KoisAlbany Medical Center, 43 New Scotland Ave, Albany, NY 12208, USA.
Geneviève BaujatUniversité de Paris, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, 75015 Paris, France; Fédération de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France.
Christopher T GordonUniversité de Paris, Imagine Institute, Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, 75015 Paris, France.
Valerie MayneDepartment of Medical Imaging, Royal Children's Hospital, Melbourne, Australia 3052.
Louise GalmicheDepartment of Pathology, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France.
Valérie SerreUniversité de Paris, Institut Jacques Monod, UMR7592 CNRS, 15 Rue Hélène Brion, 75013 Paris, France.
Nicolas GoudinUniversité de Paris, Imagine Institute, Cell Imaging, INSERM UMR 1163, 75015 Paris, France.
Mohammed ZarhrateUniversité de Paris, Imagine Institute, Structure Fédérative de Recherche Necker, Genomic Platform, INSERM UMR 1163 and INSERM US24, Centre National de la Recherche Scientifique UMS3633, 75015 Paris, France.
Christine Bole-FeysotUniversité de Paris, Imagine Institute, Structure Fédérative de Recherche Necker, Genomic Platform, INSERM UMR 1163 and INSERM US24, Centre National de la Recherche Scientifique UMS3633, 75015 Paris, France.
Cécile MassonUniversité de Paris, Imagine Institute, Bioinformatics Platform, INSERM UMR 1163, 75015 Paris, France.
Patrick NitschkéUniversité de Paris, Imagine Institute, Bioinformatics Platform, INSERM UMR 1163, 75015 Paris, France.
Frans W VerheijenDepartment of Clinical Genetics, Erasmus Medical Center, 3015 GD Rotterdam, the Netherlands.
Lynn PaisCenter for Mendelian Genomics, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA.
Anna PeletUniversité de Paris, Imagine Institute, Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, 75015 Paris, France.
Simon SadedinBrain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, 3010 Victoria, Australia.
John A PughAlbany Medical Center, 43 New Scotland Ave, Albany, NY 12208, USA.
Natasha ShurChildren's National, 111 Michigan Ave NW, Washington, D.C. 20010, USA.
Susan M WhiteVictorian Clinical Genetics Services, Murdoch Children's Research Institute and Department of Pediatrics, University of Melbourne, Melbourne, Australia 3052.
Salima El ChehadehService de Génétique Médicale, Hôpital de Hautepierre, 67098 Strasbourg, France.
John ChristodoulouBrain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, 3010 Victoria, Australia.
Valérie Cormier-DaireUniversité de Paris, Imagine Institute, Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, 75015 Paris, France; Fédération de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France.
R M W HofstraDepartment of Clinical Genetics, Erasmus Medical Center, 3015 GD Rotterdam, the Netherlands.
Stanislas LyonnetUniversité de Paris, Imagine Institute, Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, 75015 Paris, France; Fédération de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France.
Tiong Yang TanVictorian Clinical Genetics Services, Murdoch Children's Research Institute and Department of Pediatrics, University of Melbourne, Melbourne, Australia 3052.
Tania Attié-BitachFédération de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France; Université de Paris, Imagine Institute, Laboratory of Genetics and Development of the Cerebral Cortex, INSERM UMR 1163, 75015 Paris, France.
Wilhelmina S Kerstjens-FrederikseDepartment of Genetics, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.
Jeanne AmielUniversité de Paris, Imagine Institute, Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, 75015 Paris, France; Fédération de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, 75015 Paris, France.
Sophie ThomasUniversité de Paris, Imagine Institute, Laboratory of Embryology and Genetics of Malformations, INSERM UMR 1163, 75015 Paris, France. Electronic address: sophie.thomas@inserm.fr.
Inserm · FRHôpital Necker-Enfants Malades · FRRoyal Children's Hospital · AUCentre National de la Recherche Scientifique · FRErasmus MC · NLAlbany Medical Center Hospital · USThe University of Melbourne · AUBroad Institute · USChildren's National · USHôpital d'Hautepierre · FRUniversity Medical Center Groningen · NL

Funding

Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
NHGRI NIH HHS UM1 HG008900
6 · The paper itself

Abstract

The evolutionarily conserved hedgehog (Hh) pathway is essential for organogenesis and plays critical roles in postnatal tissue maintenance and renewal. A unique feature of the vertebrate Hh pathway is that signal transduction requires the primary cilium (PC) where major pathway components are dynamically enriched. These factors include smoothened (SMO) and patched, which constitute the core reception system for sonic hedgehog (SHH) as well as GLI transcription factors, the key mediators of the pathway. Here, we report bi-allelic loss-of-function variations in SMO in seven individuals from five independent families; these variations cause a wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis). Cells derived from affected individuals showed normal ciliogenesis but severely altered Hh-signal transduction as a result of either altered PC trafficking or abnormal activation of the pathway downstream of SMO. In addition, Hh-independent GLI2 accumulation at the PC tip in cells from the affected individuals suggests a potential function of SMO in regulating basal ciliary trafficking of GLI2 when the pathway is off. Thus, loss of SMO function results in abnormal PC dynamics of key components of the Hh signaling pathway and leads to a large continuum of malformations in humans.

Indexed as

AllelesSignal TransductionBase SequenceChildChild, PreschoolCiliaDevelopmental DisabilitiesFemaleHedgehog ProteinsHumansInfantMaleModels, MolecularNeoplasmsNerve Tissue ProteinsNuclear ProteinsGLI2 protein, humanGLI3 protein, humanHedgehog ProteinsNerve Tissue ProteinsNuclear ProteinsSmoothened ReceptorSMO protein, humanZinc Finger Protein Gli2Zinc Finger Protein Gli3ciliopathiesdevelopmental anomalieshedgehog signalinghuman geneticsprimary ciliumSMOsmoothened

Identifiers

PMID32413283
PMCPMC7273534
OpenAlexW3024384808

What OpenQuestion holds

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Registered trials

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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.