title: De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association.
abstract: The acronym VATER/VACTERL association describes the combination of at least three of the following congenital anomalies: vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). We aimed to identify highly penetrant de novo copy number variations (CNVs) that contribute to VATER/VACTERL association. Array-based molecular karyotyping was performed in a cohort of 41 patients with VATER/VACTERL association and 6 patients with VATER/VACTERL-like phenotype including all of the patients' parents. Three de novo CNVs were identified involving chromosomal regions 1q41, 2q37.3, and 8q24.3 comprising one (SPATA17), two (CAPN10, GPR35), and three (EPPK1, PLEC, PARP10) genes, respectively. Pre-existing data from the literature prompted us to choose GPR35 and EPPK1 for mouse expression studies. Based on these studies, we prioritized GPR35 for sequencing analysis in an extended cohort of 192 patients with VATER/VACTERL association and VATER/VACTERL-like phenotype. Although no disease-causing mutation was identified, our mouse expression studies suggest GPR35 to be involved in the development of the VATER/VACTERL phenotype. Follow-up of GPR35 and the other genes comprising the identified duplications is warranted.
authors.affiliation: 1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany [3] Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Alina
authors.initials: A
authors.lastname: Hilger
authors.forename: Charlotte
authors.initials: C
authors.lastname: Schramm
authors.forename: Tracie
authors.initials: T
authors.lastname: Pennimpede
authors.forename: Lars
authors.initials: L
authors.lastname: Wittler
authors.forename: Gabriel C
authors.initials: GC
authors.lastname: Dworschak
authors.forename: Enrika
authors.initials: E
authors.lastname: Bartels
authors.forename: Hartmut
authors.initials: H
authors.lastname: Engels
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Zink
authors.forename: Franziska
authors.initials: F
authors.lastname: Degenhardt
authors.forename: Annette M
authors.initials: AM
authors.lastname: Müller
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schmiedeke
authors.forename: Sabine
authors.initials: S
authors.lastname: Grasshoff-Derr
authors.forename: Stefanie
authors.initials: S
authors.lastname: Märzheuser
authors.forename: Stuart
authors.initials: S
authors.lastname: Hosie
authors.forename: Stefan
authors.initials: S
authors.lastname: Holland-Cunz
authors.forename: Charlotte H W
authors.initials: CH
authors.lastname: Wijers
authors.forename: Carlo L M
authors.initials: CL
authors.lastname: Marcelis
authors.forename: Iris A L M
authors.initials: IA
authors.lastname: van Rooij
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: Bernhard G
authors.initials: BG
authors.lastname: Herrmann
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Markus
authors.initials: M
authors.lastname: Draaken
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D001003:Anal Canal / Q000002:abnormalities*; D000818:Animals; D001006:Anus, Imperforate / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D004947:Esophagus / Q000002:abnormalities*; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007621:Karyotyping / Q000379:methods; D007668:Kidney / Q000002:abnormalities*; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008297:Male; D051379:Mice; D011884:Radius / Q000002:abnormalities*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D013131:Spine / Q000002:abnormalities*; D014132:Trachea / Q000002:abnormalities*
chemical_list: C513986:GPR35 protein, mouse; D043562:Receptors, G-Protein-Coupled
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