Whole exome sequencing analysis of 6 children with dilated cardiomyopathy / 中华实用儿科临床杂志

ABSTRACT

Objective:To explore the mutational loci associated with the occurrence of dilated cardiomyopathy (DCM).Methods:Six children with DCM and 3 healthy children were recruited through the " Children DCM Susceptibility Gene Research Project" for a prospective study from December 2019 to June 2021.Six patients were aged from 4 months to 14 years, including 5 girls and 1 boy.Three healthy children were aged between 3-13 years, including 2 girls and 1 boy.Whole exome sequencing was performed on the research subjects, and the pathogenic genes were identified by bioinformatics methods.At the same time, the venous blood of the first-degree relatives of the corresponding children was collected, and the region with gene mutations was subjected to next-generation sequencing.Results:A total of 4 mutational loci that might be related to DCM were identified.Case 1 was found to have a c. 2011-3C>G mutation in the jounctophiilin-2 ( JPH2) gene.The c.2011-3C>G mutation was homozygous (GG) in the child, but heterozygous (CG) in the parents.This child also had a c.G49415A mutation in the titin ( TTN) gene.This c.G49415A mutation was homozygous (AA) in the child, but heterozygous (GA) in the parents.Case 4 was found to have a c.G23033A mutation in the TTN gene.The c.G23033A mutation was heterozygous (GA) in both the subject and the father, but a wild type (GG) in the mother.Case 5 was found to have a c.16975_16978del mutation in the TTN gene.The c.16975_16978del mutation was heterozygous (TCTTC/T) in the child and the father, but a wild type (TCTTC/TCTTC) in the mother. Conclusions:A total of 4 pathogenic gene loci related to the pathogenesis of DCM are identified in this study.The finding enriches the DCM disease gene spectrum and provides targets for the implementation of precision medicine.