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Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.
Jin, Sheng Chih; Homsy, Jason; Zaidi, Samir; Lu, Qiongshi; Morton, Sarah; DePalma, Steven R; Zeng, Xue; Qi, Hongjian; Chang, Weni; Sierant, Michael C; Hung, Wei-Chien; Haider, Shozeb; Zhang, Junhui; Knight, James; Bjornson, Robert D; Castaldi, Christopher; Tikhonoa, Irina R; Bilguvar, Kaya; Mane, Shrikant M; Sanders, Stephan J; Mital, Seema; Russell, Mark W; Gaynor, J William; Deanfield, John; Giardini, Alessandro; Porter, George A; Srivastava, Deepak; Lo, Cecelia W; Shen, Yufeng; Watkins, W Scott; Yandell, Mark; Yost, H Joseph; Tristani-Firouzi, Martin; Newburger, Jane W; Roberts, Amy E; Kim, Richard; Zhao, Hongyu; Kaltman, Jonathan R; Goldmuntz, Elizabeth; Chung, Wendy K; Seidman, Jonathan G; Gelb, Bruce D; Seidman, Christine E; Lifton, Richard P; Brueckner, Martina.
Afiliação
  • Jin SC; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Homsy J; Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
  • Zaidi S; Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Lu Q; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Morton S; Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.
  • DePalma SR; Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Zeng X; Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
  • Qi H; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Chang W; Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York, USA.
  • Sierant MC; Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
  • Hung WC; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Haider S; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Zhang J; Department of Computational Chemistry, University College London School of Pharmacy, London, UK.
  • Knight J; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
  • Bjornson RD; Yale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
  • Castaldi C; Yale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
  • Tikhonoa IR; Yale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
  • Bilguvar K; Yale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
  • Mane SM; Yale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
  • Sanders SJ; Yale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA.
  • Mital S; Department of Psychiatry, University of California San Francisco, San Francisco, California, USA.
  • Russell MW; Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
  • Gaynor JW; Division of Pediatric Cardiology, University of Michigan, Ann Arbor, Michigan, USA.
  • Deanfield J; Department of Pediatric Cardiac Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • Giardini A; Department of Cardiology, University College London and Great Ormond Street Hospital, London, UK.
  • Porter GA; Department of Cardiology, University College London and Great Ormond Street Hospital, London, UK.
  • Srivastava D; Department of Pediatrics, University of Rochester Medical Center, The School of Medicine and Dentistry, Rochester, New York, USA.
  • Lo CW; Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
  • Shen Y; Roddenberry Stem Cell Center at Gladstone, San Francisco, California, USA.
  • Watkins WS; Departments of Pediatrics and Biochemistry & Biophysics, University of California, San Francisco, San Francisco, California, USA.
  • Yandell M; Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Yost HJ; Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, New York, USA.
  • Tristani-Firouzi M; Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah and School of Medicine, Salt Lake City, Utah, USA.
  • Newburger JW; Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah and School of Medicine, Salt Lake City, Utah, USA.
  • Roberts AE; USTAR Center for Genetic Discovery, University of Utah, Salt Lake City, Utah, USA.
  • Kim R; Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah and School of Medicine, Salt Lake City, Utah, USA.
  • Zhao H; Division of Pediatric Cardiology, University of Utah, Salt Lake City, Utah, USA.
  • Kaltman JR; Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Goldmuntz E; Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Chung WK; Pediatric Cardiac Surgery, Children's Hospital of Los Angeles, Los Angeles, California, USA.
  • Seidman JG; Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.
  • Gelb BD; Heart Development and Structural Diseases Branch, Division of Cardiovascular Sciences, NHLBI/NIH, Bethesda, Maryland, USA.
  • Seidman CE; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Lifton RP; Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, New York, USA.
  • Brueckner M; Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Nat Genet ; 49(11): 1593-1601, 2017 Nov.
Article em En | MEDLINE | ID: mdl-28991257
ABSTRACT
Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ∼5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ∼11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ∼3% of isolated CHD patients and ∼28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70% probability of being disease related. DNMs in ∼440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Cadeias Pesadas de Miosina / Predisposição Genética para Doença / Miosinas Cardíacas / Receptor 3 de Fatores de Crescimento do Endotélio Vascular / Fator 1 de Diferenciação de Crescimento / Cardiopatias Congênitas Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Adult / Child / Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Cadeias Pesadas de Miosina / Predisposição Genética para Doença / Miosinas Cardíacas / Receptor 3 de Fatores de Crescimento do Endotélio Vascular / Fator 1 de Diferenciação de Crescimento / Cardiopatias Congênitas Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Adult / Child / Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos