title: Contribution of genomic copy-number variations in prenatal oral clefts: a multicenter cohort study.
abstract: We sought to investigate the utility of chromosomal microarray analysis (CMA) for prenatal diagnosis of oral clefts, as compared with traditional chromosome analysis, for improved prenatal genetic counseling and discovery of a potential correlation between genotype and oral cleft.
  
  
  
  This retrospective analysis encompassed 270 prenatal oral cleft cases with documented detailed ultrasound findings and CMA results from four referral centers. Detection rates for pathogenic copy-number variants (CNVs) were calculated and compared with cases for which chromosome analysis was also performed.
  
  
  
  The overall detection rate was 14.8% (40/270) for pathogenic CNVs by CMA, 7.2% (9/125) for the nonsyndromic cases, and 21.4% (31/145) for the syndromic cases. Of the nonsyndromic cases with ultrasound soft markers, 20% (5/25) were identified with pathogenic CNVs. CMA showed an improved detection rate of 15.3% (29/190) compared with 10.5% (20/190) for chromosome analysis.
  
  
  
  This study not only highlights the improved detection of chromosomal defects by CMA in prenatal oral clefts but also deepens our understanding of oral clefts. The results suggest that CMA is highly recommended in prenatal invasive genetic testing not only for syndromic oral cleft cases but also for nonsyndromic cases with soft markers. Candidate genes including CRKL, AKAP8, SYDE1, BRD4 are worthy of further investigation regarding their role in human palatogenesis.Genet Med 18 10, 1052-1055.
authors.affiliation: Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Zhihua
authors.identifier: 0000-0003-0840-749X
authors.initials: Z
authors.lastname: Li
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington, USA.
authors.forename: Jill A
authors.identifier: 0000-0001-5664-7987
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Amber N
authors.initials: AN
authors.lastname: Pursley
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Tak Yeung
authors.initials: TY
authors.lastname: Leung
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.affiliation: Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.|Angsana Molecular & Diagnostics Laboratory (HK) Ltd., Hong Kong SAR, China.
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
mesh_terms: D002869:Chromosome Aberrations; D002972:Cleft Palate / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling; D023281:Genomics; D006801:Humans; D007621:Karyotyping; D046228:Microarray Analysis; D011247:Pregnancy; D011296:Prenatal Diagnosis