title: Whole exome sequencing and array-based molecular karyotyping as aids to prenatal diagnosis in fetuses with suspected Simpson-Golabi-Behmel syndrome.
abstract: OBJECTIVE
  Simpson-Golabi-Behmel (SGBS) syndrome type 1 and type 2 represent rare X-linked prenatal overgrowth disorders. The aim of our study is to describe the prenatal sonographic features as well as the genetic work-up.
  
  
  METHODS
  Retrospective analysis of four cases with a pre- or postnatal diagnosis of SGBS in a single tertiary referral center within a period of 4 years.
  
  
  RESULTS
  In the study period, four male fetuses with SGBS were detected. The final diagnosis was made prenatally in three cases. In all cases the second trimester anomaly scan revealed left sided congenital diaphragmatic hernia (CDH) with additional anomalies; three fetuses with SGBS type 1 showed fetal overgrowth. In two of these, whole exome sequencing showed a possible frameshift mutation and a point mutation in the gene GPC3, respectively. In the third case, multiplex ligation-dependent probe amplification (MLPA) revealed a hemizygous duplication of exon 3-7 in the gene GPC3. In the fourth case, SGBS type 2 was confirmed by array comparative genomic hybridization (CGH) of amniotic fluid cells showing a deletion of the gene OFD1.
  
  
  CONCLUSIONS
  We could demonstrate, that in the presence of a CDH, syndromes of the fetus can be increasingly differentiated by detailed sonography followed by a selective and graded molecular diagnostic using microarray techniques and whole exome sequencing. © 2016 John Wiley & Sons, Ltd.
authors: Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany.
authors: Christina
authors: C
authors: Kehrer
authors: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Alexander
authors: A
authors: Hoischen
authors: Center for Assisted Reproduction and Prenatal Diagnosis, Minden, Germany.
authors: Ralf
authors: R
authors: Menkhaus
authors: Medical Office for Human Genetics, Wiesbaden, Germany.
authors: Eva
authors: E
authors: Schwab
authors: Department of Neonatology and Pediatric Intensive Care, University of Bonn, Bonn, Germany.
authors: Andreas
authors: A
authors: Müller
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: Sarah
authors: S
authors: Kim
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: Martina
authors: M
authors: Kreiß
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: Valerie
authors: V
authors: Weitensteiner
authors: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: Alina
authors: A
authors: Hilger
authors: Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany.
authors: Christoph
authors: C
authors: Berg
authors: Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany.
authors: Anne
authors: A
authors: Geipel
authors: Department of Neonatology and Pediatric Intensive Care, University of Bonn, Bonn, Germany.|Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors: Heiko
authors: H
authors: Reutter
authors: Department of Obstetrics and Prenatal Medicine, University of Bonn, Bonn, Germany. ulrich.gembruch@ukb.uni-bonn.de.
authors: Ulrich
authors: U
authors: Gembruch
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D005320:Fetal Macrosomia / Q000209:etiology; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D005877:Gigantism / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D006330:Heart Defects, Congenital / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D065630:Hernias, Diaphragmatic, Congenital / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D007621:Karyotyping / Q000379:methods; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA; D016216:Ultrasonography, Prenatal