Copy-number variation of the glucose transporter gene SLC2A3 and congenital heart defects in the 22q11.2 deletion syndrome

Elisabeth E. Mlynarski, Molly B. Sheridan, Michael Xie, Tingwei Guo, Silvia E. Racedo, Donna M. McDonald-Mcginn, Xiaowu Gai, Eva W.C. Chow, Jacob Vorstman, Ann Swillen, Koen Devriendt, Jeroen Breckpot, Maria Cristina Digilio, Bruno Marino, Bruno Dallapiccola, Nicole Philip, Tony J. Simon, Amy E. Roberts, Małgorzata Piotrowicz, Carrie E. BeardenStephan Eliez, Doron Gothelf, Karlene Coleman, Wendy R. Kates, Marcella Devoto, Elaine Zackai, Damian Heine-Suñer, Tamim H. Shaikh, Anne S. Bassett, Elizabeth Goldmuntz, Bernice E. Morrow, Beverly S. Emanuel

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)753-764
Number of pages12
JournalAmerican journal of human genetics
Issue number5
StatePublished - May 7 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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