A novel ZIC3 mutation in a Chinese family with heterotaxy and multiple types of congenital heart defect

Prenat Diagn. 2023 Mar;43(3):275-279. doi: 10.1002/pd.6294. Epub 2022 Dec 30.


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.

MeSH terms

  • East Asian People
  • Female
  • Heart Defects, Congenital* / genetics
  • Heterotaxy Syndrome* / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Infant
  • Male
  • Mutation
  • Pregnancy
  • Prenatal Diagnosis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transposition of Great Vessels* / genetics


  • Homeodomain Proteins
  • Transcription Factors