Abstract
To identify candidate genes for intellectual disability, we performed a meta-analysis on 2,637 de novo mutations, identified from the exomes of 2,104 patient-parent trios. Statistical analyses identified 10 new candidate ID genes: DLG4, PPM1D, RAC1, SMAD6, SON, SOX5, SYNCRIP, TCF20, TLK2 and TRIP12. In addition, we show that these genes are intolerant to nonsynonymous variation and that mutations in these genes are associated with specific clinical ID phenotypes.
Publication types
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Meta-Analysis
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Review
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Research Support, Non-U.S. Gov't
MeSH terms
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Carrier Proteins / genetics
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DNA-Binding Proteins / genetics
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Disks Large Homolog 4 Protein
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Exome / genetics
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Heterogeneous-Nuclear Ribonucleoproteins / genetics
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Humans
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Intellectual Disability / genetics*
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Intracellular Signaling Peptides and Proteins / genetics
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Membrane Proteins / genetics
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Minor Histocompatibility Antigens / genetics
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Mutation / genetics*
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Phenotype
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Protein Kinases / genetics
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Protein Phosphatase 2C / genetics
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SOXD Transcription Factors / genetics
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Smad6 Protein / genetics
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Transcription Factors / genetics
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Ubiquitin-Protein Ligases / genetics
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rac1 GTP-Binding Protein / genetics
Substances
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Carrier Proteins
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DLG4 protein, human
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DNA-Binding Proteins
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Disks Large Homolog 4 Protein
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Heterogeneous-Nuclear Ribonucleoproteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Minor Histocompatibility Antigens
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RAC1 protein, human
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SMAD6 protein, human
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SON protein, human
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SOX5 protein, human
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SOXD Transcription Factors
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SYNCRIP protein, human
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Smad6 Protein
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TCF20 protein, human
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Transcription Factors
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TRIP12 protein, human
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Ubiquitin-Protein Ligases
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Protein Kinases
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protein kinase U
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PPM1D protein, human
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Protein Phosphatase 2C
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rac1 GTP-Binding Protein