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Refining analyses of copy number variation identifies specific genes associated with developmental delay.
Coe, Bradley P; Witherspoon, Kali; Rosenfeld, Jill A; van Bon, Bregje W M; Vulto-van Silfhout, Anneke T; Bosco, Paolo; Friend, Kathryn L; Baker, Carl; Buono, Serafino; Vissers, Lisenka E L M; Schuurs-Hoeijmakers, Janneke H; Hoischen, Alex; Pfundt, Rolph; Krumm, Nik; Carvill, Gemma L; Li, Deana; Amaral, David; Brown, Natasha; Lockhart, Paul J; Scheffer, Ingrid E; Alberti, Antonino; Shaw, Marie; Pettinato, Rosa; Tervo, Raymond; de Leeuw, Nicole; Reijnders, Margot R F; Torchia, Beth S; Peeters, Hilde; O'Roak, Brian J; Fichera, Marco; Hehir-Kwa, Jayne Y; Shendure, Jay; Mefford, Heather C; Haan, Eric; Gécz, Jozef; de Vries, Bert B A; Romano, Corrado; Eichler, Evan E.
Afiliação
  • Coe BP; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
  • Witherspoon K; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
  • Rosenfeld JA; Signature Genomics Laboratories, LLC, PerkinElmer, Inc., Spokane, Washington, USA.
  • van Bon BW; 1] Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands. [2] SA Pathology, North Adelaide, South Australia, Australia.
  • Vulto-van Silfhout AT; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Bosco P; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Associazione Oasi Maria Santissima, Troina, Italy.
  • Friend KL; SA Pathology, North Adelaide, South Australia, Australia.
  • Baker C; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
  • Buono S; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Associazione Oasi Maria Santissima, Troina, Italy.
  • Vissers LE; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Schuurs-Hoeijmakers JH; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Hoischen A; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Pfundt R; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Krumm N; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
  • Carvill GL; Department of Pediatrics, University of Washington, Seattle, Washington, USA.
  • Li D; Representing the Autism Phenome Project, MIND Institute, University of California, Davis, Sacramento, California, USA.
  • Amaral D; Representing the Autism Phenome Project, MIND Institute, University of California, Davis, Sacramento, California, USA.
  • Brown N; 1] Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia. [2] Barwon Child Health Unit, Barwon Health, Geelong, Victoria, Australia.
  • Lockhart PJ; 1] Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia. [2] Murdoch Childrens Research Institute, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Scheffer IE; Florey Institute, University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Alberti A; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Associazione Oasi Maria Santissima, Troina, Italy.
  • Shaw M; SA Pathology, North Adelaide, South Australia, Australia.
  • Pettinato R; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Associazione Oasi Maria Santissima, Troina, Italy.
  • Tervo R; Division of Developmental and Behavioral Pediatrics, Mayo Clinic, Rochester, Minnesota, USA.
  • de Leeuw N; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Reijnders MR; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Torchia BS; Signature Genomics Laboratories, LLC, PerkinElmer, Inc., Spokane, Washington, USA.
  • Peeters H; 1] Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium. [2] Leuven Autism Research (LAuRes), Leuven, Belgium.
  • O'Roak BJ; 1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA. [2].
  • Fichera M; 1] IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Associazione Oasi Maria Santissima, Troina, Italy. [2].
  • Hehir-Kwa JY; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Shendure J; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
  • Mefford HC; Department of Pediatrics, University of Washington, Seattle, Washington, USA.
  • Haan E; 1] SA Pathology, North Adelaide, South Australia, Australia. [2] School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
  • Gécz J; 1] SA Pathology, North Adelaide, South Australia, Australia. [2] Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia.
  • de Vries BB; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Romano C; IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Associazione Oasi Maria Santissima, Troina, Italy.
  • Eichler EE; 1] Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA. [2] Howard Hughes Medical Institute, Seattle, Washington, USA.
Nat Genet ; 46(10): 1063-71, 2014 10.
Article em En | MEDLINE | ID: mdl-25217958
ABSTRACT
Copy number variants (CNVs) are associated with many neurocognitive disorders; however, these events are typically large, and the underlying causative genes are unclear. We created an expanded CNV morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. We resequenced 26 candidate genes in 4,716 additional cases with developmental delay or autism and 2,193 controls. An integrated analysis of CNV and single-nucleotide variant (SNV) data pinpointed 10 genes enriched for putative loss of function. Follow-up of a subset of affected individuals identified new clinical subtypes of pediatric disease and the genes responsible for disease-associated CNVs. These genetic changes include haploinsufficiency of SETBP1 associated with intellectual disability and loss of expressive language and truncations of ZMYND11 in individuals with autism, aggression and complex neuropsychiatric features. This combined CNV and SNV approach facilitates the rapid discovery of new syndromes and genes involved in neuropsychiatric disease despite extensive genetic heterogeneity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Deficiências do Desenvolvimento / Predisposição Genética para Doença / Variações do Número de Cópias de DNA Tipo de estudo: Risk_factors_studies Limite: Child / Female / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Deficiências do Desenvolvimento / Predisposição Genética para Doença / Variações do Número de Cópias de DNA Tipo de estudo: Risk_factors_studies Limite: Child / Female / Humans / Male Idioma: En Ano de publicação: 2014 Tipo de documento: Article