Identification of novel significant variants of ZFPM2/FOG2 in non-syndromic Tetralogy of Fallot and double outlet right ventricle in a Chinese Han population.

Tetralogy of Fallot (TOF) and double outlet right ventricle (DORV) are two common subtypes of conotruncal defects. Recent reports have implicated mutations in the zinc finger protein, FOG family member 2 (ZFPM2/FOG2) as a cause of TOF/DORV, but no current literature focuses on the relationship between ZFPM2/FOG2 gene and non-syndromic TOF and DORV in Chinese Han population. The purpose of this study was to estimate the occurrence and the prevalence of ZFPM2/FOG2 genetic variants in Chinese Han population with non-syndromic TOF and DORV and to investigate genotype–phenotype correlations in individuals with ZFPM2/FOG2 mutations. The whole exons of ZFPM2/FOG2 were sequenced in 98 non-syndromic TOF/DORV patients and 200 control subjects. All the six variants (G2482A, G1552A, A2107C, C452T, C3239T, C1208G) changed the amino acid (p.Val828Met, p.Ala518Thr, p.Met703Leu, p.Thr151Ile, p.Ser1080Phe, p.Ala403Gly), in which four variants (G2482A, C452T, G1552A, C3239T) were not reported before and absent in control subjects. Further analysis revealed that only occurrences of variants G2482A and A2107C had statistical significance compared to the control group (P < 0.05). In conclusion, our results provide strong evidence regarding the susceptibility of the ZFPM2 gene to the development of non-syndromic TOF/DORV. It suggests that ZFPM2/FOG2 genetic variants may be a novel potential bio-markers and treatment targets for the non-syndromic TOF and DORV.