Title: Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome
Authors: Mlynarski, Elisabeth E
Sheridan, Molly B
Xie, Michael
Guo, Tingwei
Racedo, Silvia E
McDonald-McGinn, Donna M
Gai, Xiaowu
Chow, Eva W C
Vorstman, Jacob
Swillen, Ann
Devriendt, Koenraad
Breckpot, Jeroen
Digilio, Maria Cristina
Marino, Bruno
Dallapiccola, Bruno
Philip, Nicole
Simon, Tony J
Roberts, Amy E
Piotrowicz, Małgorzata
Bearden, Carrie E
Eliez, Stephan
Gothelf, Doron
Coleman, Karlene
Kates, Wendy R
Devoto, Marcella
Zackai, Elaine
Heine-Suñer, Damian
Shaikh, Tamim H
Bassett, Anne S
Goldmuntz, Elizabeth
Morrow, Bernice E
Emanuel, Beverly S ×
International Chromosome 22q11.2 Consortium #
Issue Date: May-2015
Publisher: American Society of Human Genetics
Series Title: American Journal of Human Genetics vol:96 issue:5 pages:753-64
Article number: S0002-9297(15)00108-1
Abstract: The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect. The etiology of this phenotypic variability is not currently known. We hypothesized that copy-number variants (CNVs) outside the 22q11.2 deleted region might increase the risk of being born with a CHD in this sensitized population. Genotyping with Affymetrix SNP Array 6.0 was performed on two groups of subjects with 22q11DS separated by time of ascertainment and processing. CNV analysis was completed on a total of 949 subjects (cohort 1, n = 562; cohort 2, n = 387), 603 with CHDs (cohort 1, n = 363; cohort 2, n = 240) and 346 with normal cardiac anatomy (cohort 1, n = 199; cohort 2, n = 147). Our analysis revealed that a duplication of SLC2A3 was the most frequent CNV identified in the first cohort. It was present in 18 subjects with CHDs and 1 subject without (p = 3.12 × 10(-3), two-tailed Fisher's exact test). In the second cohort, the SLC2A3 duplication was also significantly enriched in subjects with CHDs (p = 3.30 × 10(-2), two-tailed Fisher's exact test). The SLC2A3 duplication was the most frequent CNV detected and the only significant finding in our combined analysis (p = 2.68 × 10(-4), two-tailed Fisher's exact test), indicating that the SLC2A3 duplication might serve as a genetic modifier of CHDs and/or aortic arch anomalies in individuals with 22q11DS.
ISSN: 0002-9297
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Genetics of Human Development
× corresponding author
# (joint) last author

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