PUBLICATION
A novel ZIC3 gene mutation identified in patients with heterotaxy and congenital heart disease
- Authors
- Li, S., Liu, S., Chen, W., Yuan, Y., Gu, R., Song, Y., Li, J., Cao, Y., Lin, Y., Xu, J., Wang, H., Ma, D., Ma, X., Sheng, W., Huang, G.
- ID
- ZDB-PUB-180820-13
- Date
- 2018
- Source
- Scientific Reports 8: 12386 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adolescent
- Adult
- Aged
- Animals
- Child
- DNA Mutational Analysis
- Female
- Genetic Association Studies
- Genetic Predisposition to Disease
- Genotype
- Heart Defects, Congenital/diagnosis*
- Heart Defects, Congenital/genetics*
- Heterotaxy Syndrome/diagnosis*
- Heterotaxy Syndrome/genetics*
- Homeodomain Proteins/genetics*
- Homeodomain Proteins/metabolism
- Humans
- Male
- Middle Aged
- Mutation*
- Pedigree
- Phenotype
- Radiography, Thoracic
- Tomography, X-Ray Computed
- Transcription Factors/genetics*
- Transcription Factors/metabolism
- Transcriptional Activation
- Young Adult
- Zebrafish
- PubMed
- 30120289 Full text @ Sci. Rep.
Citation
Li, S., Liu, S., Chen, W., Yuan, Y., Gu, R., Song, Y., Li, J., Cao, Y., Lin, Y., Xu, J., Wang, H., Ma, D., Ma, X., Sheng, W., Huang, G. (2018) A novel ZIC3 gene mutation identified in patients with heterotaxy and congenital heart disease. Scientific Reports. 8:12386.
Abstract
Heterotaxy syndrome (HTX) is characterized by left-right (LR) asymmetry disturbances associated with severe heart malformations. However, the exact genetic cause of HTX pathogenesis remains unclear. The aim of this study was to investigate the pathogenic mechanism underlying heterotaxy syndrome. Targeted next-generation sequencing (NGS) was performed for twenty-two candidate genes correlated with LR axis development in sixty-six HTX patients from unrelated families. Variants were filtered from databases and predicted in silico using prediction programs. A total of twenty-one potential disease-causing variants were identified in seven genes. Next, we used Sanger sequencing to confirm the identified variants in the family pedigree and found a novel hemizygous mutation (c.890G > T, p.C297F) in the ZIC3 gene in a male patient that was inherited from his mother, who was a carrier. The results of functional indicated that this ZIC3 mutation decreases transcriptional activity, affects the affinity of the GLI-binding site and results in aberrant cellular localization in transfected cells. Moreover, morpholino-knockdown experiments in zebrafish demonstrated that zic3 mutant mRNA failed to rescue the abnormal phenotype, suggesting a role for the novel ZIC3 mutation in heterotaxy syndrome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping