Gene Detection And Literature Review Of A Case Of Restrictive Cardiomyopathy

Objective:(1)Define the etiology of children with primary restrictive cardiomyopathy by whole exon sequencing.(2)Assess the prognosis of the primary restrictive cardiomyopathy child by reviewing related literatures and give some recommendations for the selection of follow-up treatment options.(3)Identify the source of disease-causing mutations in children and provide reasonable genetic counseling to family members to prevent further spread of harmful mutations.(4)To evaluate the clinical significance of applying all-exome sequencing to assist in the diagnosis and treatment of restrictive cardiomyopathy in children.Methods:The clinical data of a primary restrictive cardiomyopathy family was collected and standard family map was drawn.The peripheral blood of the child and his parents were collected,genomic DNA(gDNA)was extracted from the blood and all exon sequencing was performed.The mutation sites were screened by bioinformatics analysis,and the mutation sites were verified by Sanger sequencing to identify the pathogenic mutations carried by the child.Search for relevant reports of the mutation sites in biomedical databases such as PubMed,EMBASE,CNKI,and VIP and Wanfang databases.Comprehensive analysis of the clinical data of the child has been reported,to assess the progress of the child’s disease and to provide some advice for its follow-up treatment.By consulting the online human genetics database(OMIM)and combining the parental gene sequencing results to identify the source of the disease mutation,combined with the family members’ follow-up birth plan to give reasonable genetic advice.Results:The bilateral atrial hypertrophy,ventricular septum and left ventricular wall hypertrophy,and left ventricular diastolic function were reduced,which met the diagnostic criteria for restrictive cardiomyopathy.Through the whole exon sequencing,it was found that the B626C>T(pP209L)missense mutation occurred in the BAG3 gene,and the Sanger sequencing results were consistent with the exon sequencing results.The software predicts that the mutation site is located in the highly conserved domain of BAG3 protein and is highly pathogenic.After reviewing the relevantliterature,it was found that the mutation was a reported pathogenic mutation of a restrictive cardiomyopathy.Children with restrictive cardiomyopathy carrying this mutation have a very poor prognosis,most of them have sudden death or have undergone heart transplantation.Therefore,the child should closely monitor cardiac function in the future to prevent serious cardiovascular adverse events.The OMIM database results show that the BAG3 gene is a causative gene of human genetic disease,and its genetic pattern is autosomal dominant inheritance.Because the parents’ phenotype is normal,and the sequencing results show that the two people do not carry the mutation gene,it can be inferred that the mutation source of the child is new,and the parents can continue to have healthy off spring.However,because they have already given birth to a child with a genetic mutation,there may be some factors that significantly increase the incidence of mutations in their offspring.Conclusion:(1)Restrictive cardiomyopathy seriously affects heart function in children.(2)Whole exon sequencing can efficiently and accurately detect gene mutations in children with RCM,thus clarifying the cause.(3)Whole exon sequencing technology can be used to identify the cause of RCM and to discover new types of pathogenic mutations.(4)Although full exon sequencing has broad application prospects during RCM clinical diagnosis and treatment,it still needs to be verified by Sanger sequencing.