Prenatal whole exome sequencing identified two rare compound heterozygous variants in EVC2 causing Ellis‐van Creveld syndrome.

Background: Pathogenic mutations in EVC or EVC2 gene can lead to Ellis‐van Creveld (EvC) syndrome, which is a rare autosomal recessive skeletal dysplasia disorder. This study aimed to determine pathogenic gene variations associated with EvC syndrome in fetuses showing ultrasound anomalies. Methods: A 32‐year‐old pregnant woman from Quanzhou, China was investigated. In her pregnancy examination, the fetus exhibited multiple fetal malformations, including a narrow thorax, short limbs, postaxial polydactyly, cardiac malformations, and separation of double renal pelvis. Karyotype, chromosomal microarray analysis and whole exome sequencing were performed for prenatal genetic etiology analysis. Results: Chromosome abnormalities and copy number variants were not observed in the fetus using karyotype and chromosomal microarray analysis. Using whole exome sequencing, two compound heterozygous variants NM_147127.5:c.[2484G>A(p.Trp828Ter)];[871‐2_894del] in EVC2 gene were identified in the fetus as pathogenic variants inherited from parents. Conclusions: The study is the first to identify two rare compound variants in EVC2 gene in a Chinese family using whole exome sequencing. The application of whole‐exome sequencing would be helpful in fetal etiological diagnosis with ultrasound anomalies. [ABSTRACT FROM AUTHOR]