The Gene Mutation Research In Pediatric Cardiomyopathy

Background The most coomon pediatric carimyopathies are primary cardiomyopathies,tachycardia induced cardiomyopathies,metabolic cardiomyopathies and malformation syndromes.The underlying etiology of cardiomyopathies in childhood is slowly being elucidated.Most cases of pediatric cardiomyopathies are genetic in origin.In the past,genetic evaluation for cardiomyopathies was performed by sequential screening of a very limited number of genes.Recent developments in sequencing have increased the throughput,enabling simultaneous screening of multiple genes for multiple patients in a single sequencing run.The gene panel of the cardiomyopathies appears as follow.Objective To assess the performance characteristics of a nextgeneration sequencing(NGS)assay that targets 110 well-established cardiomyopathies genes and to explore the genotype-phenotype correlation.Methods We selected 113 consecutive unrelated patients diagnosed as cardiomyopathy and aged ≤14 years old in our hospital from September 2015 to February 2017.A standardized protocol for ultra-high coverage next-generation sequencing of the well-related cardiomyopathy genes were performed in all patients.A bidirdctional sequencing of Sanger were used to their immediate family members.Results Of 113 eligible patients,37 patients diagnosed DCM,20 patients diagnosed HCM,20 patients diagnosed LVNC,7 patients diagnosed RCM,2 patients diagnosed ARVC,5 patients diagnosed TIC,3 patients diagnosed EFE,11 patients diagnosed GSDⅡ,4 patients diagnosed PCD,1 patient dianosed Danon diease,1 patient diagnosed Barth syndrome and 2 patients diagnosed Noonan syndrome.A total of 58 pathogenic and likely pathogenic mutations in 24 genes were indentified.7 patients identifed double mutations.22 mutations(37.9%)were first reported by us.11 mutations(18.9%)were de novo.The age at onset and the echocardiographic index had no significant difference between gene-positive and gene-negative patients in DCM and HCM.In LVNC,LVEF in gene-positive patients is lower than the gene-negative patients.The patients carried LMNA-E290K,TNNT2-R130C,RBM20-V1032fs,NEXN-E240Nfs*8+NEXN-T666N and MYH7-R663C+MYH7-R1050*had suffered the malignant clinical events.In the 7 patients with double mutations,4 patients had a severe clinical phenotype.All of the metabolic cardiomyopathies and malformation syndromes patients identified gene mutations.The Noonan syndrome have specific facial features,PCD and GSDⅡhave some special echocardiography signs.5 TIC patients had no pathogenic or likely pathogenic gene mutations identified.Conclusion(1)40%of the cases in pediatic cardiomyopathies carried gene mutations.The cardiomypathy-related gene panel including the genes of primary cardiomyopathies,metabolic cardiomyopathies and malformation syndromes is useful for diagnosis and differential diagnosis in pediatic cardiomyopathies.(2)Some gene mutations have correlation with the clinical manifestation.The gene mutation carriers especially in the familes had the malignant clinical events happened or carried the double mutations need to be followed-up.(3)The specific facial features and echocardiography signs can be helpful for the diagnosis of the metabolic cardiomyopathies and malformation syndromes.Etiological diagnosis including the gene mutation is important for the definite diagnosis.