Evidence map›Paper›PMID 25666757›Full record

ArticleMolecular psychiatry2015

Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy.

G McMichael, M N Bainbridge, E Haan, M Corbett, A Gardner, S Thompson, B W M van Bon, C L van Eyk, J Broadbent, C Reynolds and 10 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 1 pooled it
13.3field-weighted citation impact, top 1% 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

109 citing papers in PubMed, 1 synthesis or guideline pooled it, 235 citations in OpenAlex.

  1. Pooled it
  2. A complex of MAST1 and 14-3-3η regulates Tau phosphorylation in the developing cortex.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  8. A Phenotypic Paradigm for Cerebral Palsy Genetics.medRxiv : the preprint server for health sciences · 2026
    Article
  9. Article
  10. Article
  11. Genetic testing in cerebral palsy with clinical and neuroimaging variables.Developmental medicine and child neurology · 2025
    Article
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49 more citing papers are in PubMed but not listed here.

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

20 authors at 4 institutions in 3 countries.

G McMichaelRobinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
M N BainbridgeHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
E Haan1] South Australian Clinical Genetics Service, SA Pathology (at Women's and Children's Hospital), North Adelaide, SA, Australia [2] School of Pediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.
M Corbett1] Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia [2] School of Pediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.
A Gardner1] Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia [2] School of Pediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.
S Thompson1] School of Pediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia [2] Department of Pediatric Neurology, Women's and Children's Hospital, North Adelaide, SA, Australia.
B W M van Bon1] South Australian Clinical Genetics Service, SA Pathology (at Women's and Children's Hospital), North Adelaide, SA, Australia [2] Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
C L van EykRobinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
J BroadbentRobinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
C ReynoldsRobinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
M E O'CallaghanRobinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
L S NguyenSchool of Pediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.
D L AdelsonSchool of Molecular and Biomedical Science, The University of Adelaide, Adelaide, SA, Australia.
R RussoDepartment of Pediatric Rehabilitation, Women's and Children's Hospital, North Adelaide, SA, Australia.
S JhangianiHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
H DoddapaneniHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
D M MuznyHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
R A GibbsHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
J Gecz1] Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia [2] School of Pediatrics and Reproductive Health, The University of Adelaide, Adelaide, SA, Australia.ORCID 0000000278846861
A H MacLennanRobinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
The University of Adelaide · AUBaylor College of Medicine · USBoston Children's Hospital · USSouth Australia Pathology · AU

Funding

The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
NHGRI NIH HHS U54 HG003273
6 · The paper itself

Abstract

Cerebral palsy (CP) is a common, clinically heterogeneous group of disorders affecting movement and posture. Its prevalence has changed little in 50 years and the causes remain largely unknown. The genetic contribution to CP causation has been predicted to be ~2%. We performed whole-exome sequencing of 183 cases with CP including both parents (98 cases) or one parent (67 cases) and 18 singleton cases (no parental DNA). We identified and validated 61 de novo protein-altering variants in 43 out of 98 (44%) case-parent trios. Initial prioritization of variants for causality was by mutation type, whether they were known or predicted to be deleterious and whether they occurred in known disease genes whose clinical spectrum overlaps CP. Further, prioritization used two multidimensional frameworks-the Residual Variation Intolerance Score and the Combined Annotation-dependent Depletion score. Ten de novo mutations in three previously identified disease genes (TUBA1A (n=2), SCN8A (n=1) and KDM5C (n=1)) and in six novel candidate CP genes (AGAP1, JHDM1D, MAST1, NAA35, RFX2 and WIPI2) were predicted to be potentially pathogenic for CP. In addition, we identified four predicted pathogenic, hemizygous variants on chromosome X in two known disease genes, L1CAM and PAK3, and in two novel candidate CP genes, CD99L2 and TENM1. In total, 14% of CP cases, by strict criteria, had a potentially disease-causing gene variant. Half were in novel genes. The genetic heterogeneity highlights the complexity of the genetic contribution to CP. Function and pathway studies are required to establish the causative role of these putative pathogenic CP genes.

Indexed as

Genetic HeterogeneityAdultAnimalsCerebral PalsyCohort StudiesExomeFemaleGene LibraryGenetic Predisposition to DiseaseGestational AgeHumansMaleMutationParentsSequence Analysis, DNA

Identifiers

PMID25666757
OpenAlexW1993454819

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.