Evaluation of novel compound variants of CEP290 in prenatally suspected case of Meckel syndrome through whole exome sequencing

BACKGROUND: Meckel syndrome (MKS) is a fatal disease characterized by multisystem fibrosis during the prenatal or perinatal period. It has an autosomal recessive genetic pattern and is characterized by meningo occipital encephalocele, polycystic kidney dysplasia, polydactyly, and hepatobiliary ductal plate malformation. Germline variations in CEP290 have been shown to cause MKS4. METHODS: In this study, a 23‐year‐old Chinese woman who was 18 weeks pregnant was examined. The pregnancy was terminated due to occipital meningocele and enlarged cystic dysplastic kidney revealed by ultrasonography. In addition, the patient had a history of adverse pregnancy whereby the fetus presented with double kidney enlargement. Karyotype analysis and chromosomal microarray examination (CMA) were carried out using amniotic fluid samples. Whole exome sequencing (WES) was performed using tissue specimens of the aborted fetus. RESULTS: Karyotype and CMA analyses showed normal results. However, compound heterozygous mutations of CEP290 c.3175dup and CEP290 c.1201dup were detected through WES. CEP290 c.1201dup is a novel heterozygous mutation of CEP290 that has not been reported previously. CONCLUSIONS: The findings of this study provide information on the correlation between MKS phenotype and genotype in CEP290. In addition, these findings indicate that WES is an effective method for detecting genetic causes of multiple structural defects especially those showing normal karyotype and CMA results.