基因检测在肥厚型心肌病患者优生优育和治疗中的指导作用

The guiding role of genetic testing in prepotency and management of hypertrophic cardiomyopathy patients

目的:评价基因检测在指导肥厚型心肌病(HCM)女性患者受孕方式选择及发现有患病风险的一级家属家族成员的意义与价值。方法:对1例39岁女性患者进行详细临床评估及遗传基因检测,并对其家族成员进行特定性突变基因检测,根据检测结果指导患者选择合适受孕方式,评估家族成员患病风险,并对其提供临床咨询。结果:超声心动图提示HCM,基因检测发现心肌肌钙蛋白I(TNNI3)基因c.700g>a杂合子突变,突变位点处在TNNI3基因保守区域。给予患者植入式体内自动除颤器置入作为一级预防,并建议其通过健康女性卵子捐献体外受精方式再次生育。4位家族成员进行特定突变检测,未发现相同突变,避免了不必要的临床评估及长期随访。结论:对于已知先证者致病基因突变,家族成员进行特定性突变基因检测,不但能够对受累个体提供重要临床咨询,并且能指导其家族成员及后代将来的管理与治疗。

Objective：To evaluate the role and significance of genetic screening in the selection of conception methods in female patients with hypertrophic cardiomyopathy（HCM） and detecting the family members who wereat the risk of HCM. Method：A 39 year-old female patient whose father and son had history of sudden death wished to be pregnant and was seeking medical consultation.Detailed clinical assessment and genetic testing were conducted for her,and her family members underwent mutation-specific genetic testing.According to the results of genetic testing,the correct method of conception was selected.The risk of HCM was assessed and clinical consultation was provided for her family members. Result：Echocardiogram showed the manifestation of HCM.A pathogenic heterozygous mutation c.700 g〉a in a highly conservative site in TNNI3 was identified,which was not found in 200 normal control chromosomes.Because of the high sudden cardiac death（SCD） risk of c.700 g〉a mutation,ICD was implanted to prevent SCD and in vitro fertilization using a healthy female donor was suggested for the patient.The same mutation was absent in other 4 family members,which made them not need for extensive clinical investigations or long-term follow-up. Conclusion：Genetic screening appears cost effective in family members with a known mutation,provides an important information about the affected individual,and can facilitate the future management of family members and offspring.