Evidence map›Paper›PMID 40016860›Full record

ArticleMolecular autism2025

Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice.

Andreea D Pantiru, Stijn Van de Sompele, Clemence Ligneul, Camille Chatelain, Christophe Barrea, Jason P Lerch, Beatrice M Filippi, Serpil Alkan, Elfride De Baere, Jamie Johnston and 1 more

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In one paragraph

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

0numbers the graph read from it
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

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

1 citing paper in PubMed.

  1. 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

11 authors.

Andreea D PantiruSchool of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.ORCID 0000-0001-6419-5298
Stijn Van de SompeleCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.ORCID 0000-0002-3294-0668
Clemence LigneulWellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3SR, UK.ORCID 0000-0001-5673-3009
Camille ChatelainDepartment of Human Genetics, University Hospital of Liege, Liege, Belgium.ORCID 0009-0008-4731-2163
Christophe BarreaAutism Resource Centre of Liege, University of Liege, Liege, Belgium.ORCID 0000-0002-4523-2898
Jason P LerchWellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3SR, UK.ORCID 0000-0001-6164-2881
Beatrice M FilippiSchool of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.ORCID 0000-0002-8816-1559
Serpil AlkanDepartment of Human Genetics, University Hospital of Liege, Liege, Belgium.ORCID 0000-0003-1677-0272
Elfride De BaereCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium.ORCID 0000-0002-5609-6895
Jamie Johnston *School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.ORCID 0000-0002-9928-989X
Steven J Clapcote *School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK. S.J.Clapcote@leeds.ac.uk.ORCID 0000-0002-6662-5690

Funding

Biotechnology and Biological Sciences Research Council BB/R019401/1Medical Research Council MR/R014736/1
6 · The paper itself

Abstract

backgroundIntellectual developmental disorder with autism and dysmorphic facies (IDDADF) is a rare syndromic intellectual disability (ID) caused by homozygous disruption of PDZD8 (PDZ domain-containing protein 8), an integral endoplasmic reticulum (ER) protein. All four previously identified IDDADF cases exhibit autistic behavior, with autism spectrum disorder (ASD) diagnosed in three cases. To determine whether autistic behavior is a common outcome of PDZD8 disruption, we studied a third family with biallelic mutation of PDZD8 (family C) and further characterized PDZD8-deficient (Pdzd8

methodsHomozygosity mapping, whole-exome sequencing, and cosegregation analysis were used to identify the PDZD8 variant responsible for IDDADF, including diagnoses of ASD, in consanguineous family C. To assess the in vivo effect of PDZD8 disruption on social responses and related phenotypes, behavioral, structural magnetic resonance imaging, and microscopy analyses were conducted on the Pdzd8

resultsThe discovery of a third family with IDDADF caused by biallelic disruption of PDZD8 permitted identification of a core clinical phenotype consisting of developmental delay, ID, autism, and facial dysmorphism. In addition to impairments in social recognition and social odor discrimination, Pdzd8 LIMITATIONS: The total number of known cases of PDZD8-related IDDADF remains low. Some mouse experiments in the study did not use balanced numbers of males and females. The assessment of ER stress and mitochondrial fusion markers did not extend beyond mRNA levels.

conclusionsOur finding that the Pdzd8

Indexed as

AllelesAutistic DisorderAnimalsAutism Spectrum DisorderBehavior, AnimalChildDisease Models, AnimalExome SequencingFemaleHomozygoteHumansIntellectual DisabilityMaleMiceMutationPedigreeAutism spectrum disorderIntellectual disabilityOlfactory behaviorPDZD8Social discrimination

Identifiers

PMID40016860
PMCPMC11866840

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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.