TY - JOUR
T1 - De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association
AU - Hilger, Alina
AU - Schramm, Charlotte
AU - Pennimpede, Tracie
AU - Wittler, Lars
AU - Dworschak, Gabriel C.
AU - Bartels, Enrika
AU - Engels, Hartmut
AU - Zink, Alexander M.
AU - Degenhardt, Franziska
AU - Müller, Annette M.
AU - Schmiedeke, Eberhard
AU - Grasshoff-Derr, Sabine
AU - Märzheuser, Stefanie
AU - Hosie, Stuart
AU - Holland-Cunz, Stefan
AU - Wijers, Charlotte Hw
AU - Marcelis, Carlo Lm
AU - Van Rooij, Iris Alm
AU - Hildebrandt, Friedhelm
AU - Herrmann, Bernhard G.
AU - Nöthen, Markus M.
AU - Ludwig, Michael
AU - Reutter, Heiko
AU - Draaken, Markus
N1 - Funding Information:
We thank all patients and their parents for their participation in this study. We thank the German self-help organization for providing people with anorectal malformations (SoMA e.V.). Grants were sponsored by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF; grant no. 01GM08107) and The BONFOR program of the University of Bonn (grant no. O-149.0093 to CS, grant no. O-149.0099 to EB, and grant no. O-149.0096 to GCD). TP, LW, EB, ES, SG-D, SM, SH, SH-C, BGH, MMN, ML, HR, and MD are members of the ‘Network for the Systematic Investigation of the Molecular Causes, Clinical Implications and Psychosocial Outcome of Congenital Uro-Rectal Malformations (CURE-Net)’, which is supported by a research grant from the BMBF.
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
KW - CNV analysis
KW - GPR35
KW - SNP array
KW - VATER/VACTERL association
KW - candidate genes
KW - microaberrations
UR - https://www.scopus.com/pages/publications/84887627106
U2 - 10.1038/ejhg.2013.58
DO - 10.1038/ejhg.2013.58
M3 - Article
C2 - 23549274
AN - SCOPUS:84887627106
SN - 1018-4813
VL - 21
SP - 1377
EP - 1382
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 12
ER -