Evidence map›Paper›PMID 39706195›Full record

ArticleAmerican journal of human genetics2025

Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus.

Marcello Scala, Clarrisa A Bradley, Jennifer L Howe, Brett Trost, Nelson Bautista Salazar, Carole Shum, Marla Mendes, Miriam S Reuter, Evdokia Anagnostou, Jeffrey R MacDonald and 25 more

Abstract read
PubMed Full text at PMC Publisher
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. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Marcello ScalaDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genoa, Italy; UOC Genetica Medica, IRCCS Giannina Gaslini, Genoa, Italy. Electronic address: mscala.md@gmail.com.
Clarrisa A BradleyThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
Jennifer L HoweThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Brett TrostThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Nelson Bautista SalazarThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Carole ShumThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Marla MendesThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Miriam S ReuterThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Evdokia AnagnostouDepartment of Pediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Program in Neurosciences and Mental Health, The Hospital for Sick Children and Department of Physiology, University of Toronto, Toronto, ON, Canada.
Jeffrey R MacDonaldThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Sangyoon Y KoThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
Paul W FranklandBloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada; Department of Psychology and Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Jessica CharleboisAzrieli Centre for Autism Research, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada.
Mayada ElsabbaghAzrieli Centre for Autism Research, Montreal Neurological Institute-Hospital, McGill University, Montreal, QC, Canada.
Leslie GrangerDepartment of Genetics and Metabolism, Randall Children's Hospital, Portland, OR 97227, USA.
George AnadiotisDepartment of Genetics and Metabolism, Randall Children's Hospital, Portland, OR 97227, USA.
Verdiana PullanoDepartment of Medical Sciences, University of Torino, Torino, Italy.
Alfredo BruscoDepartment of Neurosciences Rita Levi-Montalcini, University of Turin, 10126 Turin, Italy; Medical Genetics Unit, Città della Salute e della Scienza University Hospital, Torino, Italy.
Roberto KellerAdult Autism Centre DSM ASL Città di Torino, 10138 Turin, Italy.
Sarah ParisottoCenter for Genetic and Genomic Medicine, Hackensack University Medical Center, Hackensack, NJ, USA.
Helio F PedroCenter for Genetic and Genomic Medicine, Hackensack University Medical Center, Hackensack, NJ, USA.
Laina LuskEpilepsy Neurogenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Pamela Pojomovsky McDonnellEpilepsy Neurogenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Ingo HelbigEpilepsy Neurogenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Sureni V MullegamaGeneDx, Gaithersburg, MD, USA.
Undiagnosed Diseases Network
Emilie D DouineDepartment of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
Rosario Ivetth CoronaDepartment of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
Bianca E RussellDepartment of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
Stanley F NelsonDepartment of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
Claudio GrazianoDipartimento MeLabeT, AUSL della Romagna, Pievesestina di Cesena, Cesena, Italy.
Maria SchwabCenter for Genetic and Genomic Medicine, Hackensack University Medical Center, Hackensack, NJ, USA.
Laurie SimoneCenter for Genetic and Genomic Medicine, Hackensack University Medical Center, Hackensack, NJ, USA.
Federico ZaraDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa, Genoa, Italy; UOC Genetica Medica, IRCCS Giannina Gaslini, Genoa, Italy.
Stephen W SchererThe Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; McLaughlin Centre, Toronto, ON M5G 0A4, Canada. Electronic address: stephen.scherer@sickkids.ca.

Funding

A computational phenotyping approach to characterize neurogenetic disordersR01NS131512 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI Ingo Helbig · 2023 to 2026
$2.8M
Joint analysis of genomic and electronic medical record data to assess outcomes and drug response in pediatric epilepsiesK02NS112600 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI HELBIG, INGO · 2020 to 2024
$963k
UCLA clinical site for the investigation of undiagnosed disordersU01NS134356 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-AGOSTO, JULIAN, NELSON, STANLEY F. · 2023 to 2023
$936k
NINDS NIH HHS K02 NS112600NINDS NIH HHS R01 NS131512NINDS NIH HHS U01 NS134356
6 · The paper itself

Abstract

Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males. This locus includes the three-exon PTCHD1, an adjacent multi-isoform long noncoding RNA (lncRNA) named PTCHD1-AS (spanning ∼1 Mb), and a poorly characterized single-exon RNA helicase named DDX53 that is intronic to PTCHD1-AS. While the relationship between PTCHD1/PTCHD1-AS and ASD is being studied, the role of DDX53 has not been comprehensively examined, in part because there is no apparent functional murine ortholog. Through clinical testing, here, we identified 8 males and 2 females with ASD from 8 unrelated families carrying rare, predicted damaging or loss-of-function variants in DDX53. Additionally, we identified a family consisting of a male proband and his affected mother with high-functioning autism, both harboring a gene deletion involving DDX53 and exons of the noncoding RNA PTCHD1-AS. Then, we examined databases, including the Autism Speaks MSSNG and Simons Foundation Autism Research Initiative, as well as population controls. We identified 26 additional individuals with ASD harboring 19 mostly maternally inherited, rare, damaging DDX53 variations, including two variants detected in families from the original clinical analysis. Our findings in humans support a direct link between DDX53 and ASD, which will be important in clinical genetic testing. These same autism-related findings, coupled with the observation that a functional orthologous gene is not found in mice, may also influence the design and interpretation of murine modeling of ASD.

Indexed as

Autism Spectrum DisorderDEAD-box RNA HelicasesAdolescentAdultChildChild, PreschoolChromosomes, Human, XFemaleGenetic LociGenetic Predisposition to DiseaseGenetic VariationHumansMalePedigreeRNA, Long NoncodingDEAD-box RNA HelicasesRNA, Long Noncodingautismautism spectrum disorderDDX53MSSNGneurodevelopmental disordersnon-coding RNAPTCHD1-ASRNA helicaseSFARIXp22.11 locus

Identifiers

PMID39706195
PMCPMC11739878

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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.