Evidence map›Paper›PMID 34737294›Full record

ArticleNPJ genomic medicine2021

A recurrent SHANK3 frameshift variant in Autism Spectrum Disorder.

Livia O Loureiro, Jennifer L Howe, Miriam S Reuter, Alana Iaboni, Kristina Calli, Delnaz Roshandel, Iva Pritišanac, Alan Moses, Julie D Forman-Kay, Brett Trost and 24 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Molecular Screening Reveals De Novo Loss-of-FunctionInternational journal of molecular sciences · 2025
    Article
  5. Review
  6. Article
  7. Dynamic glycosylation remodeling in neurological disorders.Frontiers in molecular neuroscience · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Early-onset catatonia associated withFrontiers in psychiatry · 2023
    Article
  15. 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

34 authors at 11 institutions in 3 countries.

Livia O Loureiro *Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Jennifer L Howe *Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Miriam S ReuterCanada's Genomics Enterprise (CGEn), The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-8662-6685
Alana IaboniHolland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
Kristina CalliDepartment of Medical Genetics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0002-8632-983X
Delnaz RoshandelGenetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-4902-8587
Iva PritišanacProgram in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Alan MosesDepartment of Cell & Systems Biology, University of Toronto, Toronto, ON, Canada.
Julie D Forman-KayProgram in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Brett TrostGenetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-4863-7273
Mehdi ZarreiGenetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Olivia RennieGenetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-9441-978X
Lynette Y S LauGenome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Christian R MarshallGenome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-4003-7671
Siddharth SrivastavaDepartment of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Brianna GodlewskiDepartment of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Elizabeth D ButtermoreDepartment of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3194-5413
Mustafa SahinDepartment of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7044-2953
Dean HartleyAutism Speaks, New York, NY, USA.
Thomas FrazierAutism Speaks and Department of Psychology, John Carroll University, Cleveland, OH, USA.
Jacob VorstmanDepartment of Psychiatry, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-1677-3126
Stelios GeorgiadesDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
Suzanne M E LewisDepartment of Medical Genetics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
Peter SzatmariDepartment of Psychiatry, University of Toronto, Toronto, ON, Canada.
Clarrisa A Lisa BradleyGenetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-3117-5263
Anne-Claude TabetHuman Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, Université de Paris, F-75015, Paris, France.ORCID http://orcid.org/0000-0003-2910-7744
Marjolaine WillemsService de Génétique clinique, CH de Chambéry, Chambéry, France.
Serge LumbrosoBiochimie et Biologie Moléculaire, CHU Nimes, Univ. Montpellier, Nimes, France.
Amélie PitonInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, UMR7104, Institut National de la Santé et de la Recherche Médicale, U964, Université de Strasbourg, Illkirch, France.
James LespinasseService de Génétique clinique, CH de Chambéry, Chambéry, France.
Richard DelormeHuman Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, Université de Paris, F-75015, Paris, France.
Thomas BourgeronHuman Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, Université de Paris, F-75015, Paris, France.
Evdokia AnagnostouHolland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
Stephen W SchererGenetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada. stephen.scherer@sickkids.ca.ORCID http://orcid.org/0000-0002-8326-1999
Hospital for Sick Children · CAUniversity of Toronto · CABoston Children's Hospital · USCentre National de la Recherche Scientifique · FRAutism Speaks · USCentre Hospitalier Métropole Savoie · FRUniversity of British Columbia · CACentre for Addiction and Mental Health · CAHolland Bloorview Kids Rehabilitation Hospital · CAMcMaster University · CAUniversité de Montpellier · FR

Funding

Toward better characterization and clinical trial readiness for targeting neuropsychiatric manifestations in PTEN pathogenic variantsU54NS092090 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI MUSTAFA SAHIN · 2014 to 2026
$20.1M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
NICHD NIH HHS P50 HD105351NINDS NIH HHS U54 NS092090
6 · The paper itself

Abstract

Autism Spectrum Disorder (ASD) is genetically complex with ~100 copy number variants and genes involved. To try to establish more definitive genotype and phenotype correlations in ASD, we searched genome sequence data, and the literature, for recurrent predicted damaging sequence-level variants affecting single genes. We identified 18 individuals from 16 unrelated families carrying a heterozygous guanine duplication (c.3679dup; p.Ala1227Glyfs*69) occurring within a string of 8 guanines (genomic location [hg38]g.50,721,512dup) affecting SHANK3, a prototypical ASD gene (0.08% of ASD-affected individuals carried the predicted p.Ala1227Glyfs*69 frameshift variant). Most probands carried de novo mutations, but five individuals in three families inherited it through somatic mosaicism. We scrutinized the phenotype of p.Ala1227Glyfs*69 carriers, and while everyone (17/17) formally tested for ASD carried a diagnosis, there was the variable expression of core ASD features both within and between families. Defining such recurrent mutational mechanisms underlying an ASD outcome is important for genetic counseling and early intervention.

Identifiers

PMID34737294
PMCPMC8568906
OpenAlexW3209613800

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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.