Abstract：Objective Whole exome sequencing was used to capture and screen genetic mutations in neonatal congenital heart disease. Methods We selected 6 children with severe congenital heart disease who had ventricular septal defect and atrial septal defect diagnosed by neonatology specialists from January 2014 to April 2018 in Lanzhou Maternal and Child Health Hospital. Blood samples of 6 children and their parents were collected, and the mutant genes were captured by whole exome sequencing. The dbSNP, HapMap, and internal databases of VEP and BGI were used to annotate and screen the pathogenic mutations of congenital heart disease. The mutations were verified by Sanger sequencing. Results According to the screening criteria, de novo mutations were found in the three of the six families. Three of them have missense mutations, namelyFH2 domain-containing protein 1 (FHDC1)(c.1977G>C;p.Gln659His)、bromodomain-containing protein 4 (BRD4)(c.3797A>C;p.Glu1266Ala)、hexokinase 3(HK3)(c.397C>G;p.Leu133Val), as well as one gene splice site mutated to sprouty related EVH1 domain-containing protein 2 (SPRED2)(c.373+1G>T). ConclusionFHDC1 (c.1977G> c), BRD4 (c.3797A>c), HK3 (c.397C>G), and SPRED2 (c.373+1G>T) may be deleterious de novo mutations for congenital heart disease.
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