SRCAP基因变异致扩张型心肌病1例家系分析并文献复习

Study on a family of dilated cardiomyopathy caused by SRCAP gene mutation

目的分析SRCAP基因变异致扩张型心肌病(DCM)家系基因型与临床表型的相关性。方法回顾分析1例特发性DCM患儿的临床资料,利用全外显子测序技术检测致病基因,以Sanger测序验证,利用I-TASSER软件预测致病基因对蛋白质结构及功能的影响。结果患儿男性,16月龄,临床特征为反复呼吸道感染、心肌酶高、心肌收缩力减低、高乳酸血症、语言发育落后,无恶性心律失常。全外显子测序发现SRCAP c.452-453 del,pPhe 151 Cysfs*71基因变异,为新发杂合变异,常染色体显性遗传,以往未有报道。SRCAP基因第151位半胱氨酸在不同物种之间具有高度保守性。I-TASSER软件预测野生型蛋白质3230残基,变异体蛋白质220残基;亲疏水性分析野生型亲水性Sum(求和)(5:3226)=-1449.44,变异体亲水性Sum(求和)(5:216)=-126.55。结论SRCAP基因c.452-453 del(pPhe 151 Cysfs*71)变异可导致肽链合成提前终止、蛋白质结构截短及亲疏水性发生明显改变,结合患儿临床表型此变异可能是DCM新发现的致病变异。

Objective To analyze the correlation between the genotype and clinical phenotype of the family with dilated cardiomyopathy caused by SRCAP gene mutation.Methods To retrospectively analyze the clinical data of a child with idiopathic dilated cardiomyopathy,use whole exome sequencing technology to find the pathogenic gene,and verify with Sanger sequencing,use I-TASSER software to predict whether the pathogenic gene affects protein structure and Features.Results The whole exome sequencing of a 16-month male child with DCM found that SRCAP c.452-453 del,pPhe 151 Cysfs*71 gene mutations were found.The family verified that the mutations were new heterozygous mutations through Sanger sequencing technology,and the inheritance mode was autosomal dominant.Genetic.Cysteine at position 151 of SRCAP gene is highly conserved among different species.I-TASSER software predicts 3230 residues of wild-type protein and 220 residues of mutant protein.Hydrophilicity analysis wild-type hydrophilic Sum(5:3226)=-1449.44,mutant hydrophilic Sum(5:216)=-126.55.Conclusion SRCAPc.452-453 del,pPhe 151 Cysfs*71 gene mutation is a new site mutation,which leads to premature termination of peptide chain synthesis,protein structure truncation and significant changes in hydrophilicity and hydrophobicity.Combining genotype and clinical phenotype analysis,consider The SRCAPc.452-453 del mutation at this site is a new pathogenic mutation of DCM.The clinical characteristics were recurrent respiratory tract infection,high myocardial enzyme spectrum,decreased myocardial contractility,hyperlactic disease,backward language development,no malignant arrhythmia.