title: Prenatal diagnosis and molecular cytogenetic characterization of chromosome 22q11.2 deletion syndrome associated with congenital heart defects.
abstract: OBJECTIVE
  To report prenatal diagnosis of 22q11.2 deletion syndrome in a pregnancy with congenital heart defects in the fetus.
  
  
  METHODS
  A 26-year-old, primigravid woman was referred for counseling at 24 weeks of gestation because of abnormal ultrasound findings of fetal congenital heart defects. The Level II ultrasound revealed a singleton fetus with heart defects including overriding aorta, small pulmonary artery, and ventricular septal defect. Cordocentesis was performed. The DNA extracted from the cord blood was analyzed by multiplex ligation-dependent amplification (MLPA). The MLPA showed deletion in the DiGeorge syndrome (DGS) critical region of chromosome 22 low copy number repeat (LCR) 22-A∼C. Conventional cytogenetic analysis revealed a normal male karyotype. Repeated amniocentesis and cordocentesis were performed. Whole-genome array comparative genomic hybridization (aCGH) on cord blood was performed. aCGH detected a 3.07-Mb deletion at 22q11.21. Conventional cytogenetic analysis of cultured amniocytes revealed a karyotype 46,XY. Metaphase fluorescence in situ hybridization (FISH) analysis on cultured amniocytes confirmed an interstitial 22q11.2 deletion.
  
  
  CONCLUSIONS
  Prenatal ultrasound findings of congenital heart defects indicate that the fetuses are at increased risk for chromosome abnormalities. Studies for 22q11.2 deletion syndrome should be considered adjunct to conventional karyotyping. Although FISH has become a standard procedure for diagnosis of 22q11.2 deletion syndrome, MLPA can potentially diagnose a broader spectrum of abnormalities, and aCGH analysis has the advantage of refining the 22q11.2 deletion breakpoints and detecting uncharacterized chromosome rearrangements or genomic imbalances.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Kuo
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: cpc_mmh@yahoo.com.
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Liang-Kai
authors.initials: LK
authors.lastname: Wang
authors.affiliation: GenePhile Bioscience Laboratory, Ko's Obstetrics and Gynecology, Taipei, Taiwan.
authors.forename: Tsang-Ming
authors.initials: TM
authors.lastname: Ko
authors.affiliation: Taiji Fetal Medicine Center, Taipei, Taiwan.
authors.forename: Tung-Yao
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Schu-Rern
authors.initials: SR
authors.lastname: Chern
authors.affiliation: Gene Biodesign Co. Ltd, Taipei, Taiwan.
authors.forename: Peih-Shan
authors.initials: PS
authors.lastname: Wu
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Chang
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging* / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging* / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D059785:Karyotype; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014463:Ultrasonography
keywords: 22q11.2 deletion syndrome; congenital heart defects; prenatal diagnosis