Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome
Copyright policy )Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome
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.
- University of Colorado Health United States
- Utrecht University Netherlands
- University of Geneva Switzerland
- University of Pennsylvania United States
- KU Leuven Belgium
Male, Biomedical and clinical sciences, Thoracic, Aorta, Thoracic, Aorta, Thoracic/physiopathology, Cardiovascular, Medical and Health Sciences, International Chromosome 22q11.2 Consortium, Congenital, Cardiovascular Medicine and Haematology, 2.1 Biological and endogenous factors, Genetics(clinical), Aetiology, Aorta, Heart Defects, Pediatric, Genetics & Heredity, Glucose Transporter Type 3, Single Nucleotide, Biological Sciences, Biological sciences, Heart Disease, Heart Defects, Congenital/genetics/physiopathology, Female, Adult, Heart Defects, Congenital, DNA Copy Number Variations, Genotype, DNA Copy Number Variations/genetics, Glucose Transporter Type 3/genetics, Polymorphism, Single Nucleotide, Rare Diseases, Research Support, N.I.H., Extramural, Clinical Research, DiGeorge Syndrome/genetics/physiopathology, Journal Article, Genetics, DiGeorge Syndrome, Humans, Polymorphism, Biomedical and Clinical Sciences, Prevention, Health sciences, Adult; Aorta, Thoracic; DNA Copy Number Variations; DiGeorge Syndrome; Female; Genotype; Glucose Transporter Type 3; Heart Defects, Congenital; Humans; Male; Polymorphism, Single Nucleotide, 616.89, Congenital Structural Anomalies, ddc: ddc:616.89
Male, Biomedical and clinical sciences, Thoracic, Aorta, Thoracic, Aorta, Thoracic/physiopathology, Cardiovascular, Medical and Health Sciences, International Chromosome 22q11.2 Consortium, Congenital, Cardiovascular Medicine and Haematology, 2.1 Biological and endogenous factors, Genetics(clinical), Aetiology, Aorta, Heart Defects, Pediatric, Genetics & Heredity, Glucose Transporter Type 3, Single Nucleotide, Biological Sciences, Biological sciences, Heart Disease, Heart Defects, Congenital/genetics/physiopathology, Female, Adult, Heart Defects, Congenital, DNA Copy Number Variations, Genotype, DNA Copy Number Variations/genetics, Glucose Transporter Type 3/genetics, Polymorphism, Single Nucleotide, Rare Diseases, Research Support, N.I.H., Extramural, Clinical Research, DiGeorge Syndrome/genetics/physiopathology, Journal Article, Genetics, DiGeorge Syndrome, Humans, Polymorphism, Biomedical and Clinical Sciences, Prevention, Health sciences, Adult; Aorta, Thoracic; DNA Copy Number Variations; DiGeorge Syndrome; Female; Genotype; Glucose Transporter Type 3; Heart Defects, Congenital; Humans; Male; Polymorphism, Single Nucleotide, 616.89, Congenital Structural Anomalies, ddc: ddc:616.89
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