title: Copy number variants in short children born small for gestational age.
abstract: OBJECTIVE
  In addition to genome-wide association studies (GWAS), height-associated genes may be uncovered by studying individuals with extreme short or tall stature.
  
  
  METHODS
  Genome-wide analysis for copy number variants (CNVs), using single nucleotide polymorphism (SNP) arrays, was performed in 49 index cases born small for gestational age with persistent short stature. Segregation analysis was performed, and genes in CNVs were compared with information from GWAS, gene expression in rodents' growth plates, and published information.
  
  
  RESULTS
  CNVs were detected in 13 cases. In 5 children a known cause of short stature was found: UPD7, UPD14, a duplication of the SHOX enhancer region, an IGF1R deletion, and a 22q11.21 deletion. In the remaining 8 cases, potential pathogenic CNVs were detected, either de novo (n = 1), segregating (n = 2), or not segregating with short stature (n = 5). Bioinformatic analysis of the de novo and segregating CNVs suggested that HOXD4, AGPS, PDE11A, OSBPL6, PRKRA and PLEKHA3, and possibly DGKB and TNFRSF11B are potential candidate genes. A SERPINA7 or NRK defect may be associated with an X-linked form of short stature.
  
  
  CONCLUSIONS
  SNP arrays detected 5 known causes of short stature with prenatal onset and suggested several potential candidate genes.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Hermine A
authors.initials: HA
authors.lastname: van Duyvenvoorde
authors.forename: Jan B
authors.initials: JB
authors.lastname: van Klinken
authors.forename: Janina
authors.initials: J
authors.lastname: Caliebe
authors.forename: Cathy A J
authors.initials: CA
authors.lastname: Bosch
authors.forename: Julian C
authors.initials: JC
authors.lastname: Lui
authors.forename: Antoinet C J
authors.initials: AC
authors.lastname: Gijsbers
authors.forename: Egbert
authors.initials: E
authors.lastname: Bakker
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Wilma
authors.initials: W
authors.lastname: Oostdijk
authors.forename: Monique
authors.initials: M
authors.lastname: Losekoot
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Baron
authors.forename: Gerhard
authors.initials: G
authors.lastname: Binder
authors.forename: Michael B
authors.initials: MB
authors.lastname: Ranke
authors.forename: Claudia A L
authors.initials: CA
authors.lastname: Ruivenkamp
mesh_terms: D000818:Animals; D056915:DNA Copy Number Variations; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007236:Infant, Small for Gestational Age; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide