Aims: A couple was referred for prenatal counseling at gestational age 21 weeks for revealed situs inversus with levocardia (HP:0,031,592), atrial situs inversus (HP:0,011,538), congenitally corrected transposition of the great arteries (ccTGA, HP:0,011,540) with ventricular septal defect (HP:0,001,629) and right aortic arch (HP:0,012,020). The couple had multiple prior pregnancies with complex congenital heart defects (CHDs, HP:0,001,627) in male fetuses. Testing was initiated to identify any fetal abnormality. The genetic cause of the observed prenatal defects was investigated.
Materials and methods: Whole exome sequencing and Sanger sequencing were performed on DNA extracted from parental blood samples and skeletal muscle tissue of the aborted fetuses.
Results: A pathogenic hemizygous missense variant in ZIC3 (NM_003413.4: c.895 T > C) associated with X-linked heterotaxy-1 (HTX1) and multiple types of congenital heart defect-1 (CHTD1) (OMIM #306955) was identified, which was inherited from the mother.
Conclusion: ZIC3 encodes a highly conserved zinc-finger protein that is highly correlated with CHDs. The present study of a Han Chinese family with CHDs expands the mutation spectrum of ZIC3 and provides further evidence that ZIC3 plays important roles in CHDs.
© 2022 John Wiley & Sons Ltd.