Information de reference pour ce titreAccession Number: | 01445366-201211000-00024.
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Author: | Herman, Sean B. 1; Guo, Tingwei 1; McGinn, Donna M. McDonald 2; Blonska, Anna 1,3; Shanske, Alan L. 4; Bassett, Anne S. 5,6; Chow, Eva W.C. 5,6; Bowser, Mark 2; Sheridan, Molly 2; Beemer, Frits 7; Devriendt, Koen 8; Swillen, Ann 8; Breckpot, Jeroen 8; Digilio, Cristina M. 9; Marino, Bruno 10; Dallapiccola, Bruno 9; Carpenter, Courtney 11; Zheng, Xin 12; Johnson, Jacob 1; Chung, Jonathan 1; Higgins, Anne Marie 13; Philip, Nicole 14; Simon, Tony 15; Coleman, Karlene 16; Heine-Suner, Damian 17; Rosell, Jordi 17; Kates, Wendy 18; Devoto, Marcella 2; Zackai, Elaine 2; Wang, Tao 19; Shprintzen, Robert 13; Emanuel, Beverly S. 2; Morrow, Bernice E. 1*; and the International Chromosome 22q11.2 Consortium
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Institution: | (1) Department of Genetics, Albert Einstein College of Medicine, Bronx, New York (2) Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia and Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania (3) Department of Ophthalmology, Harkness Eye Institute, Columbia University, New York, New York (4) Center for Craniofacial Disorders, Children's Hospital at Montefiore Medical Center, Bronx, New York (5) Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (6) Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada (7) Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands (8) Center for Human Genetics, University of Leuven, Leuven, Belgium (9) Medical Genetics, Bambino Gesu Hospital, Rome, Italy (10) Department of Pediatrics, La Sapienza University of Rome, Rome, Italy (11) Department of Surgery, Montefiore Medical Center, Bronx, New York (12) Research Informatics Core of Einstein-Montefiore Institute for Clinical and Translational Research, Albert Einstein College of Medicine Bronx, New York (13) The Virtual Center for Velo-Cardio-Facial Syndrome, Syracuse, New York (14) Department of Medical Genetics, AP-HM and University of Mediterranee, Timone Children's Hospital, Marseille, France (15) M.I.N.D. Institute, Department of Psychiatry and Behavioral Sciences, University of California, Davis, California (16) Children's Healthcare of Atlanta, Atlanta, Georgia (17) Genetics Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain (18) Department of Psychiatry and Behavioral Sciences, and Program in Neuroscience, SUNY Upstate Medical University, Syracuse, New York (19) Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
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Title: | |
Source: | American Journal Of Medical Genetics -A. 158A(11):2781-2787, November 2012.
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Abstract: | : Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000-1/4,000 live births. Approximately 9-11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown. The TBX1 gene, a member of the T-box transcription factor gene family, lies within the 22q11.2 region that is hemizygous in patients with 22q11DS. Inactivation of one allele of Tbx1 in the mouse does not result in CP, but inactivation of both alleles does. Based on these data, we hypothesized that DNA variants in the remaining allele of TBX1 may confer risk to CP in patients with 22q11DS. To test the hypothesis, we evaluated TBX1 exon sequencing (n = 360) and genotyping data (n = 737) with respect to presence (n = 54) or absence (n = 683) of CP in patients with 22q11DS. Two upstream SNPs (rs4819835 and rs5748410) showed individual evidence for association but they were not significant after correction for multiple testing. Associations were not identified between DNA variants and haplotypes in 22q11DS patients with CP. Overall, this study indicates that common DNA variants in TBX1 may be nominally causative for CP in patients with 22q11DS. This raises the possibility that genes elsewhere on the remaining allele of 22q11.2 or in the genome could be relevant.
Copyright (C) 2012 John Wiley & Sons, Inc.
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Author Keywords: | 22q11.2 deletion syndrome; TBX1 sequencing; cleft palate; genomic disorder.
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Language: | English.
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Document Type: | Research Articles.
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Journal Subset: | Life & Biomedical Sciences. Science.
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ISSN: | 1552-4825
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DOI Number: | https://dx.doi.org/10.1002/ajmg....- ouverture dans une nouvelle fenêtre
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