title: Prenatal diagnosis and molecular cytogenetic characterization of a 1.07-Mb microdeletion at 5q35.2-q35.3 associated with NSD1 haploinsufficiency and Sotos syndrome.
abstract: OBJECTIVE
  To present prenatal diagnosis and molecular cytogenetic characterization of a de novo 5q35 microdeletion associated with Sotos syndrome.
  
  
  METHODS
  This was the first pregnancy of a 29-year-old woman. The pregnancy was uneventful until 27 weeks of gestation when left ventriculomegaly was first noted. At 31 weeks of gestation, polyhydramnios, macrocephaly, and ventriculomegaly were prominent on ultrasound, and left pyelectasis and bilateral ventriculomegaly were diagnosed on magnetic resonance imaging. The woman underwent amniocentesis and cordocentesis at 32 weeks of gestation. Conventional cytogenetic analysis was performed using cultured amniocytes and cord blood lymphocytes. Array comparative genomic hybridization (aCGH) was performed on uncultured amniocytes and parental blood. Metaphase fluorescence in situ hybridization (FISH) was performed on cultured lymphocytes.
  
  
  RESULTS
  Conventional cytogenetics revealed a karyotype of 46,XX. aCGH on uncultured amniocytes revealed a de novo 1.07-Mb microdeletion at 5q35.2-q35.3 encompassing NSD1. Metaphase FISH analysis on the cord blood lymphocytes confirmed the deletion at 5q35.2. The postnatal phenotype was consistent with Sotos syndrome.
  
  
  CONCLUSIONS
  Fetuses with Sotos syndrome may present macrocephaly, polyhydramnios, ventriculomegaly, and pyelectasis in the third trimester. aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome.
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; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Chen-Ju
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Schu-Rern
authors.initials: SR
authors.lastname: Chern
authors.affiliation: Department of Radiology, Mackay Memorial Hospital Hsinchu Branch, Hsinchu, Taiwan; Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Liu
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.
authors.forename: Yen-Ni
authors.initials: YN
authors.lastname: Chen
authors.affiliation: Gene Biodesign Co. Ltd, Taipei, Taiwan.
authors.forename: Peih-Shan
authors.initials: PS
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Dai-Dyi
authors.initials: DD
authors.lastname: Town
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Chen
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chien-Wen
authors.initials: CW
authors.lastname: Yang
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Bioengineering, Tatung University, Taipei, Taiwan.
authors.forename: Wayseen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D020732:Cytogenetic Analysis; D005260:Female; D005819:Genetic Markers; D057895:Haploinsufficiency; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D058495:Sotos Syndrome / Q000175:diagnosis* / Q000235:genetics
chemical_list: D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human
keywords: 5q35 microdeletion; NSD1 haploinsufficiency; Sotos syndrome; array comparative genomic hybridization; prenatal diagnosis