Journal Article

Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability

Kamsteeg, Erik-Jan, Pfundt, Rolph, Rinne, Tuula, Reijnders, Margot R F, van der Burgt, Ineke, de Vries, Bert B A, Rump, Patrick, Lelieveld, Stefan H, Yntema, Helger G, Vissers, Lisenka E L M, Bongers, Ernie M H F, Veltman, Joris A, Brunner, Han G, Gilissen, Christian, Stegmann, Alexander P A, de Vries, Petra, Löhner, Katharina, Stevens, Servi J C, Willemsen, Marjolein H, Nelen, Marcel R, Vreeburg, Maaike, Kleefstra, Tjitske

2016

Overview

The authors analyzed the exome sequences of 2,104 intellectual disability patients and their parents. They identified 10 novel candidate genes associated with specific clinical phenotypes. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 45 / 45/23 / 631/208/366 / 631/208/514/2254 / Animal Genetics and Genomics / Behavioral Sciences / Biological Techniques / Biomedicine / brief-communication / Carrier Proteins - genetics / Disks Large Homolog 4 Protein / DNA-Binding Proteins - genetics / Exome - genetics / Exome sequencing / Gene mutation / Genetic aspects / Heterogeneous-Nuclear Ribonucleoproteins - genetics / Humans / Intellectual disabilities / Intellectual Disability - genetics / Intracellular Signaling Peptides and Proteins - genetics / Membrane Proteins - genetics / Minor Histocompatibility Antigens - genetics / Mutation - genetics / Neurobiology / Neurosciences / Phenotype / Protein Kinases - genetics / Protein Phosphatase 2C - genetics / rac1 GTP-Binding Protein - genetics / Risk factors / Smad6 Protein - genetics / SOXD Transcription Factors - genetics / Systematic review / Transcription Factors - genetics / Ubiquitin-Protein Ligases - genetics