title: Retrospective study of prenatal ultrasound findings in newborns with a Noonan spectrum disorder.
abstract: OBJECTIVE
  Noonan spectrum disorders (NSDs) occur in 1:1000-2500 live births. Currently, there are no guidelines for prenatal molecular genetic testing for NSDs. Recent studies recommend prenatal testing for NSDs when ultrasonography detects two or more associated abnormalities. A stronger association between ultrasound findings and NSDs would enable more informed prenatal genetic testing.
  
  
  METHODS
  A total of 212 newborns (0-12 weeks) with prenatal ultrasound findings and a clinical suspicion of a NSD were referred for molecular genetic testing. Of these, 159/212 newborns tested had a single ultrasound abnormality and 53/212 newborns had two or more. Testing was performed by either a microarray-based resequencing assay or next generation sequencing of RAS/MAPK pathway genes associated with NSDs. Prenatal ultrasound findings in positive and negative cases were compared.
  
  
  RESULTS
  A disease-causing variant was identified in 21.7% (46/212) of newborns tested. Of these positive cases, 67.4% (31/46) had only one ultrasound abnormality reported. The rate of detecting a disease-causing variant in cases with one ultrasound finding was 19.5% (31/159), which was not significantly different (p-value = 0.36) than that in cases with two or more ultrasound findings (28.3%; 15/53).
  
  
  CONCLUSIONS
  Prenatal molecular testing for NSDs should be considered even in the presence of a single associated abnormal ultrasound finding. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Departments of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.|Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA, USA.|Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City-WR, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Fahad
authors.initials: F
authors.lastname: Hakami
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA, USA.
authors.forename: Mitchell W
authors.initials: MW
authors.lastname: Dillon
authors.affiliation: Departments of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.|Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lebo
authors.affiliation: Departments of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.|Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Mason-Suares
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009634:Noonan Syndrome / Q000000981:diagnostic imaging / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies; D020837:SOS1 Protein / Q000235:genetics; D016216:Ultrasonography, Prenatal
chemical_list: C117307:KRAS protein, human; D008565:Membrane Proteins; D020837:SOS1 Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)