Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.

Autor: Stessman HA; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Xiong B; Department of Genome Sciences, University of Washington, Seattle, Washington, USA.; Department of Forensic Medicine and Institute of Brain Research, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Coe BP; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Wang T; State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China., Hoekzema K; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Fenckova M; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Kvarnung M; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden., Gerdts J; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA., Trinh S; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA., Cosemans N; Centre for Human Genetics, KU Leuven and Leuven Autism Research (LAuRes), Leuven, Belgium., Vives L; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Lin J; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Turner TN; Department of Genome Sciences, University of Washington, Seattle, Washington, USA., Santen G; Department of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, the Netherlands., Ruivenkamp C; Department of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, the Netherlands., Kriek M; Department of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, the Netherlands., van Haeringen A; Department of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, the Netherlands., Aten E; Department of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, the Netherlands., Friend K; School of Medicine and the Robinson Research Institute, the University of Adelaide at the Women's and Children's Hospital, Adelaide, South Australia, Australia.; Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia., Liebelt J; South Australian Clinical Genetics Service, SA Pathology (at the Women's and Children's Hospital), Adelaide, South Australia, Australia., Barnett C; South Australian Clinical Genetics Service, SA Pathology (at the Women's and Children's Hospital), Adelaide, South Australia, Australia., Haan E; School of Medicine and the Robinson Research Institute, the University of Adelaide at the Women's and Children's Hospital, Adelaide, South Australia, Australia.; South Australian Clinical Genetics Service, SA Pathology (at the Women's and Children's Hospital), Adelaide, South Australia, Australia., Shaw M; School of Medicine and the Robinson Research Institute, the University of Adelaide at the Women's and Children's Hospital, Adelaide, South Australia, Australia., Gecz J; School of Medicine and the Robinson Research Institute, the University of Adelaide at the Women's and Children's Hospital, Adelaide, South Australia, Australia.; Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia., Anderlid BM; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden., Nordgren A; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden., Lindstrand A; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden., Schwartz C; Center for Molecular Studies, J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, South Carolina, USA., Kooy RF; Department of Medical Genetics, University of Antwerp, Antwerp, Belgium., Vandeweyer G; Department of Medical Genetics, University of Antwerp, Antwerp, Belgium., Helsmoortel C; Department of Medical Genetics, University of Antwerp, Antwerp, Belgium., Romano C; Unit of Pediatrics &Medical Genetics, IRCCS Associazione Oasi Maria Santissima, Troina, Italy., Alberti A; Unit of Pediatrics &Medical Genetics, IRCCS Associazione Oasi Maria Santissima, Troina, Italy., Vinci M; Laboratory of Medical Genetics, IRCCS Associazione Oasi Maria Santissima, Troina, Italy., Avola E; Unit of Pediatrics &Medical Genetics, IRCCS Associazione Oasi Maria Santissima, Troina, Italy., Giusto S; Unit of Neurology, IRCCS Associazione Oasi Maria Santissima, Troina, Italy., Courchesne E; Department of Neurosciences, UC San Diego Autism Center, School of Medicine, University of California San Diego, La Jolla, California, USA., Pramparo T; Department of Neurosciences, UC San Diego Autism Center, School of Medicine, University of California San Diego, La Jolla, California, USA., Pierce K; Department of Neurosciences, UC San Diego Autism Center, School of Medicine, University of California San Diego, La Jolla, California, USA., Nalabolu S; Department of Neurosciences, UC San Diego Autism Center, School of Medicine, University of California San Diego, La Jolla, California, USA., Amaral DG; MIND Institute and the University of California Davis School of Medicine, Sacramento, California, USA., Scheffer IE; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia.; Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia., Delatycki MB; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia.; Victorian Clinical Genetics Services, Parkville, Victoria, Australia.; Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Lockhart PJ; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia.; Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Hormozdiari F; Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, California, USA., Harich B; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Castells-Nobau A; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Xia K; State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China., Peeters H; Centre for Human Genetics, KU Leuven and Leuven Autism Research (LAuRes), Leuven, Belgium., Nordenskjöld M; Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden., Schenck A; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands., Bernier RA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA., Eichler EE; Department of Genome Sciences, University of Washington, Seattle, Washington, USA.; Howard Hughes Medical Institute, Seattle, Washington, USA.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2017 Apr; Vol. 49 (4), pp. 515-526. Date of Electronic Publication: 2017 Feb 13.
DOI: 10.1038/ng.3792
Abstrakt: Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most of the related pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 cases and >2,867 controls. We identified 91 genes, including 38 new NDD genes, with an excess of de novo mutations or private disruptive mutations in 5.7% of cases. Drosophila functional assays revealed a subset with increased involvement in NDDs. We identified 25 genes showing a bias for autism versus intellectual disability and highlighted a network associated with high-functioning autism (full-scale IQ >100). Clinical follow-up for NAA15, KMT5B, and ASH1L highlighted new syndromic and nonsyndromic forms of disease.
Databáze: MEDLINE