title: Phenotypic predictors and final diagnoses in patients referred for RASopathy testing by targeted next-generation sequencing.
abstract: RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms. Next-generation sequencing (NGS)-based panels have widespread acceptance as a diagnostic tool for RASopathies.
  
  
  
  The first 126 patients evaluated by clinical examination and the NGS RASopathy panel at the Children's Hospital of Philadelphia were enrolled. We calculated diagnosis rate, correlated reported clinical findings with positive or negative test results, and identified final molecular diagnoses in 28/96 patients who tested negative for RASopathies.
  
  
  
  Twenty-four patients had pathogenic variants on the RASopathy panel, for a diagnostic yield of 19%. Reported features of pulmonic stenosis and ptosis were significantly correlated with a positive test result; no reported features were significantly correlated with a negative test result. We identified 27 different alternative diagnoses for patients originally suspected of having RASopathies.
  
  
  
  This study provides information that can assist in guiding differential diagnosis and genetic testing for patients suspected of having a RASopathy disorder.Genet Med advance online publication 20 October 2016.
authors.affiliation: Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.|Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Elizabeth J
authors.identifier: 0000-0001-5748-3507
authors.initials: EJ
authors.lastname: Bhoj
authors.affiliation: Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Qiaoning
authors.identifier: 0000-0002-5890-5756
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ahrens-Nicklas
authors.affiliation: Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Kajia
authors.initials: K
authors.lastname: Cao
authors.affiliation: Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.|Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Minjie
authors.identifier: 0000-0002-5788-3962
authors.initials: M
authors.lastname: Luo
authors.affiliation: Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Tischler
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.|Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Matthew A
authors.identifier: 0000-0002-1542-1305
authors.initials: MA
authors.lastname: Deardorff
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.|Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Zackai
authors.affiliation: Division of Genomic Diagnostics and Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.|Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Avni B
authors.initials: AB
authors.lastname: Santani
mesh_terms: D056685:Costello Syndrome / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D044542:LEOPARD Syndrome / Q000235:genetics*; D020935:MAP Kinase Signaling System; D009634:Noonan Syndrome / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies; D018631:ras Proteins / Q000378:metabolism
chemical_list: D018631:ras Proteins