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Clinical exome sequencing efficacy and phenotypic expansions involving anomalous pulmonary venous return.
Huth, Emily A; Zhao, Xiaonan; Owen, Nichole; Luna, Pamela N; Vogel, Ida; Dorf, Inger L H; Joss, Shelagh; Clayton-Smith, Jill; Parker, Michael J; Louw, Jacoba J; Gewillig, Marc; Breckpot, Jeroen; Kraus, Alison; Sasaki, Erina; Kini, Usha; Burgess, Trent; Tan, Tiong Y; Armstrong, Ruth; Neas, Katherine; Ferrero, Giovanni B; Brusco, Alfredo; Kerstjens-Frederikse, Wihelmina S; Rankin, Julia; Helvaty, Lindsey R; Landis, Benjamin J; Geddes, Gabrielle C; McBride, Kim L; Ware, Stephanie M; Shaw, Chad A; Lalani, Seema R; Rosenfeld, Jill A; Scott, Daryl A.
Afiliación
  • Huth EA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Zhao X; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Owen N; Baylor Genetics, Houston, TX, USA.
  • Luna PN; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Vogel I; Baylor Genetics, Houston, TX, USA.
  • Dorf ILH; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
  • Joss S; Department of Clinical Medicine, Aarhus University, 8000, Aarhus, C, Denmark.
  • Clayton-Smith J; Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
  • Parker MJ; West of Scotland Genomics Service, Queen Elizabeth University Hospital, Glasgow, G51 4TF, UK.
  • Louw JJ; Manchester Centre For Genomic Medicine, Manchester University Hospitals, Manchester, M13 9WL, UK.
  • Gewillig M; University of Manchester, Manchester, M13 9PL, UK.
  • Breckpot J; Department of Clinical Genetics, Sheffield, Children's Hospital, UK.
  • Kraus A; Pediatric Cardiology Maastricht University Medical Centre, Maastricht, The Netherlands.
  • Sasaki E; Department of Cardiovascular Sciences KU Leuven, Leuven, Belgium.
  • Kini U; Pediatric Cardiology University Hospitals Leuven, Leuven, Belgium.
  • Burgess T; Center for Human Genetics, University Hospitals Leuven, Catholic University, Leuven, Belgium.
  • Tan TY; Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, LS7 4SA, UK.
  • Armstrong R; Oxford Centre for Genomic Medicine, Oxford University Hospital, Oxford, OX3 7HE, UK.
  • Neas K; Oxford Centre for Genomic Medicine, Oxford University Hospital, Oxford, OX3 7HE, UK.
  • Ferrero GB; Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
  • Brusco A; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
  • Kerstjens-Frederikse WS; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
  • Rankin J; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia.
  • Helvaty LR; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
  • Landis BJ; East Anglian Medical Genetics Service, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
  • Geddes GC; Genetic Health Service NZ, Wellington, New Zealand.
  • McBride KL; Department of Clinical and Biological Sciences, University of Torino, Orbassano, Italy.
  • Ware SM; Department of Medical Sciences, University of Torino, Torino, Italy.
  • Shaw CA; Città della Salute e della Scienza University Hospital, Torino, Italy.
  • Lalani SR; Department Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Rosenfeld JA; Peninsula Clinical Genetics Service, Exeter, UK.
  • Scott DA; Indiana University School of Medicine, Indianapolis, IN, USA.
Eur J Hum Genet ; 31(12): 1430-1439, 2023 12.
Article en En | MEDLINE | ID: mdl-37673932
Anomalous pulmonary venous return (APVR) frequently occurs with other congenital heart defects (CHDs) or extra-cardiac anomalies. While some genetic causes have been identified, the optimal approach to genetic testing in individuals with APVR remains uncertain, and the etiology of most cases of APVR is unclear. Here, we analyzed molecular data from 49 individuals to determine the diagnostic yield of clinical exome sequencing (ES) for non-isolated APVR. A definitive or probable diagnosis was made for 8 of those individuals yielding a diagnostic efficacy rate of 16.3%. We then analyzed molecular data from 62 individuals with APVR accrued from three databases to identify novel APVR genes. Based on data from this analysis, published case reports, mouse models, and/or similarity to known APVR genes as revealed by a machine learning algorithm, we identified 3 genes-EFTUD2, NAA15, and NKX2-1-for which there is sufficient evidence to support phenotypic expansion to include APVR. We also provide evidence that 3 recurrent copy number variants contribute to the development of APVR: proximal 1q21.1 microdeletions involving RBM8A and PDZK1, recurrent BP1-BP2 15q11.2 deletions, and central 22q11.2 deletions involving CRKL. Our results suggest that ES and chromosomal microarray analysis (or genome sequencing) should be considered for individuals with non-isolated APVR for whom a genetic etiology has not been identified, and that genetic testing to identify an independent genetic etiology of APVR is not warranted in individuals with EFTUD2-, NAA15-, and NKX2-1-related disorders.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Cimitarra / Anomalías Múltiples / Cardiopatías Congénitas Límite: Animals Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Cimitarra / Anomalías Múltiples / Cardiopatías Congénitas Límite: Animals Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido