目的 探讨1例扩张型心肌病(DCM)患儿的临床表型及遗传学特征。 方法 收集2020年4月28日就诊于郑州儿童医院的1例患儿的临床资料，并对其进行家系全外显子组测序(trio-WES)，对候选变异进行Sanger测序验证。以"FHL2"作为关键词，检索1997年1月1日至2021年10月31日PubMed数据库收录的文献，同时在ClinVar数据库中检索FHL2变异作为补充支持，分析基因变异与临床特征的对应关系。 结果 患儿为女性，就诊时为5月龄，临床特征为左心室增大、收缩功能减低。基因测序发现其FHL2基因存在杂合错义变异c.391C>T(p.Arg131Cys)，其父母未携带相同的变异。根据美国医学遗传学与基因组学学会(ACMG)变异相关指南，c.391C>T(p.Arg131Cys)被升级为可能致病性变异(PS2+PM2_Supporting+PP3+PP5)。通过文献检索，共发现10例FHL2基因变异的患者，其中6例表现为DCM，2例表现为肥厚型心肌病(HCM)，2例表现为不明原因猝死(SUD)。变异位于FHL2蛋白LIM 3结构域的患者均表现为HCM，位于LIM 0 ~ 2、LIM 4结构域者则主要表现为DCM。 结论 FHL2基因杂合错义变异c.391C>T(p.Arg131Cys)可能是患儿DCM的原因。上述发现强调了trio-WES在疾病诊断和遗传咨询中的重要性。 Objective To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM). Methods Clinical data of the child who had presented at Zhengzhou Children′s Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES)was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. " FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features. Results The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c. 391C>T (p.Arg131Cys) inFHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of ten patients with FHL2 gene variants have been reported by previous literature, six of them presented with DCM, two with hypertrophic cardiomyopathy (HCM), and two with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c. 391C>T (p.Arg131Cys) has been identified in a child with DCM, though this variant has not been validated among the patient′s family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c. 391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+ PM2_Supporting+ PP3+ PP5). Conclusion The heterozygous missense variant of c. 391C>T (p.Arg131Cys) in theFHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of trio-WES in the clinical diagnosis and genetic counseling.
Abstract
Objective To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM). Methods Clinical data of the child who had presented at Zhengzhou Children′s Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES)was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. " FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features. Results The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c. 391C>T (p.Arg131Cys) inFHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of ten patients with FHL2 gene variants have been reported by previous literature, six of them presented with DCM, two with hypertrophic cardiomyopathy (HCM), and two with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c. 391C>T (p.Arg131Cys) has been identified in a child with DCM, though this variant has not been validated among the patient′s family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c. 391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+ PM2_Supporting+ PP3+ PP5). Conclusion The heterozygous missense variant of c. 391C>T (p.Arg131Cys) in theFHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of trio-WES in the clinical diagnosis and genetic counseling.
万方数据