Background
The most prevalent cyanotic congenital heart disease (CHD) phenotype is tetralogy of Fallot (TOF). Rare genetic variations have been identified as significant risk factors for CHD. Thus, this research sought to identify the pathogenic variations and molecular etiologies of TOF.
Methods
This study employed whole-exome sequencing (WES) and Sanger sequencing to identify pathogenic variations in DNA samples from patients with TOF. The pathogenicity of the variations was predicted using an in-silico approach.
Results
We enrolled 17 patients with TOF in this study. Among these patients, 14 had mutations in TOF-related genes, including
GJB2
,
TBX15
,
CTNS
,
SPINK1
,
GATA6
,
PRIMOL
,
GDF15
,
SLC17A9
,
AIFM1
,
FOXC2
,
KLF13
,
ABCA4
,
CPA6
,
FKBP10
,
ASPA
,
SBF1
,
HBA2
,
IGLL1
,
GNE
, and
KLHL10
. We also gathered WES data from three participants without TOF, who comprised the control group, but no variations were found in the indicated genes. Further analysis showed that the patients with
FKBP10
and
GNE
variants had more serious clinical symptoms. Sanger sequencing confirmed that the two variants were heterozygous in TOF patients.
Conclusions
We identified several genetic variants associated with TOF and confirmed that
FKBP10
and
GNE
variants were associated with TOF severity. The findings of this study help researchers and clinicians on genetic counseling with the verification of the potential of WES in detecting TOF and help implement early interventions for patients with TOF.