Abstract 13234: 1q21.1 Microduplications are Strongly Associated with Tetralogy of Fallot and 1q21.1 Microdeletions are Associated with Other Congenital Heart Defects
BACKGROUND: Microdeletions and microduplications of 1q21.1 have been associated with variable paediatric phenotypes. A previous study of 512 non-syndromic Tetralogy of Fallot (TOF) patients found 1q21.1 duplications in four patients and a deletion in one patient. We aimed to replicate these findings in a larger cohort of non-syndromic TOF and other types of congenital heart defects (CHD).
METHODS: We examined the ~1.3Mb critical region in 1q21.1 locus using a combination of Illumina 660W-Q and Affymetrix 6.0 SNP platforms as well as Multiplex Ligation Probe Amplification in 984 patients with idiopathic, non-syndromic Tetralogy of Fallot and 1467 patients with other isolated CHDs. All patients included in the study have been previously screened for DiGeorge rearrangements and major chromosomal aberrations. Additionally, we examined the frequency of 1q21.1 rearrangements in 6760 controls.
RESULTS: We identified nine TOF probands with 1q21.1 duplications and three non-TOF probands with 1q21.1 deletions. One of the duplications was de novo, three duplications were inherited from a normal parent and inheritance is unknown in the remaining patients. Our examination of the 1q21.1 region in 6760 controls revealed four deletions and two duplications. Another published study reported a frequency of one duplication and no deletions in a total of 4737 control individuals. Combining these controls gives a population frequency of 3/11497 for 1q21.1 microduplications and 4/11497 for 1q21.1 microdeletions.
CONCLUSION: 1q21.1 microduplications are strongly associated with isolated TOF phenotype (13/1496 vs. 3/11497; P=2.1x10-10), but the reciprocal microdeletions are not (P=0.45). In contrast, 1q21.1 microdeletions, but not microduplications, are associated with isolated non-TOF CHD (3/1467 vs. 4/11497; P=0.04).
- © 2011 by American Heart Association, Inc.