X-chromosomal copy number variants in patients with coarctation of the aorta

Introduction: Coarctation of the aorta occurs in 6-8% of all newborns with congenital heart disease and is more frequent in male patients. In 90%, CoA represents a non-syndromic malformation but can also be associated with syndromal disorders mainly Ullrich-Turner syndrome, where CoA is detected in 15-20% of all patients.

Methods: 70 non-syndromic patients with isolated CoA and 3 families (n=13) with 6 CoA patients were genotyped using Affimetrix Genome Wide SNP/CNV 6.0 array and compared to 605 controls. Linkage analysis for all three families was performed. CNV segments were confirmed by MLPA analysis.

Results: We identified a significant abundance of large X-chromosomal CNVs in male patients (p=0.01). Total CNV count on the autosomes showed no significant change between CoA patients and controls. Further candidate genes were identified in the sporadic cohort and the families which were absent or extremely rare (p<0.01) in 605 controls, but need further investigation.

Conclusions: Our analysis illustrates that changes on the gonosomes, mainly the X-chromosome may play an important role even in non-syndromic CoA pathogenesis. Our findings could explain that CoA is more common in male patients due to changes on the X-chromosome. Further analysis to confirm this hypothesis is needed.