Identification of two novel genetic variants for Ellis-van Creveld syndrome from a Chinese family through whole exome sequencing.

OBJECTIVE

This study conducted genetic testing and analysis on the fetal tissue of a terminated pregnancy to clarify the cause of the fetal abnormalities.

METHODS

A fetus with multiple malformations detected during mid-pregnancy was terminated. Trio whole exome sequencing (Trio-WES) was performed on the fetal tissue. The identified gene variants were verified from parents' blood samples using Sanger sequencing.

RESULTS

Prenatal ultrasound indicated that the fetus had an atrioventricular septal defect, thoracic narrowing, short and angulated long bones of the limbs, polydactyly of the hands, and right clubfoot. The high-throughput sequencing results showed that the fetus had a heterozygous splicing variant c.939+1G>A and a heterozygous frameshift deletion variant c.528delC (p. Ser177Alafs19) in the Ellis-van Creveld (EVC) gene. Sanger sequencing confirmed that the maternal variant c.939+1G>A and the paternal variant c.528delC (p. Ser177Alafs19) were the sources of the two EVC gene variants in the fetus. Combined with the genetic analysis and prenatal ultrasound findings, this family was diagnosed with Ellis-van Creveld syndrome.

CONCLUSION

Two novel causative genetic variants for EVC syndrome were identified. The findings would expand the mutational spectrum of the EVC gene and demonstrate that whole-exome sequencing is a powerful tool for the clinical diagnosis of genetically heterogeneous diseases.