title: Further evidence for deletions in 7p14.1 contributing to nonsyndromic cleft lip with or without cleft palate.
abstract: BACKGROUND
  Nonsyndromic cleft with or without cleft palate (nsCL/P) is a common birth defect. Although genome-wide association studies (GWAS) have identified numerous risk variants, a considerable fraction of the genetic heritability remains unknown. The aim of the present study was to replicate a previous finding that de novo deletions in a 62 kb region of chromosome 7p14 are a risk factor for nsCL/P, using an independent cohort.
  
  
  METHODS
  Data from a published case-control GWAS cohort of 399 patients and 1318 controls were used. Copy number variant (CNV) detection in the 62 kb candidate region of 7p14 was performed using QuantiSNP. Putative CNVs in probands were verified and validated by quantitative polymerase chain reaction. Segregation analyses were performed in family members for whom DNA was available.
  
  
  RESULTS
  Within the 62 kb candidate region, a deletion of 7.4 kb showed association with nsCL/P (13/387 cases, 20/1300 controls, plowest = 0.024, odds ratio = 2.22). In all families with a sporadic case (n = 3), the deletion occurred de novo. In multiplex families, both incomplete segregation and incomplete penetrance were observed.
  
  
  CONCLUSIONS
  The present data support the hypothesis that deletions at 7p14 are a common risk factor for nsCL/P. Genome-wide CNV analyses in nsCL/P cohorts are warranted to explore the functional relevance of these deletions and their contribution to nsCL/P, and to determine exact breakpoints. Birth Defects Research (Part A) 106:767-772, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Genomics, Life, and Brain Center, University of Bonn, Bonn, Germany.|Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Klamt
authors.affiliation: Department of Genomics, Life, and Brain Center, University of Bonn, Bonn, Germany.|Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: Department of Genomics, Life, and Brain Center, University of Bonn, Bonn, Germany.|Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Böhmer
authors.affiliation: Department of Genomics, Life, and Brain Center, University of Bonn, Bonn, Germany.|Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Hoebel
authors.affiliation: Department of Orthodontics, University of Bonn, Bonn, Germany.
authors.forename: Lina
authors.initials: L
authors.lastname: Gölz
authors.affiliation: Department of Genomics, Life, and Brain Center, University of Bonn, Bonn, Germany.|Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Becker
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Zink
authors.affiliation: Department of Genomics, Life, and Brain Center, University of Bonn, Bonn, Germany.|Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Draaken
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hemprich
authors.affiliation: Department of Oral and Maxillo-Facial Surgery, University of Cologne, Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Scheer
authors.affiliation: Department of Cleft Lip and Cleft Palate Surgery, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Gül
authors.initials: G
authors.lastname: Schmidt
authors.affiliation: Department of Oral and Maxillo-Facial-Plastic Surgery, University of Bonn, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Martini
authors.affiliation: Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.affiliation: Department of Genomics, Life, and Brain Center, University of Bonn, Bonn, Germany.|Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Degenhardt
authors.affiliation: Department of Genomics, Life, and Brain Center, University of Bonn, Bonn, Germany. kerstin.ludwig@uni-bonn.de.|Institute of Human Genetics, University of Bonn, Bonn, Germany. kerstin.ludwig@uni-bonn.de.
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
mesh_terms: D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics; D030561:Databases, Nucleic Acid; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D012307:Risk Factors
keywords: congenital malformation; copy number variants; de novo; orofacial cleft; replication study