肥厚性心肌病RAF1 c.770C>T基因突变1例并文献复习

A NOVEL MUTATION OF RAF1 c.770C>T IN HYPERTROPHIC CARDIOMYOPATHY:A CASE REPORT AND LITERATURE REVIEW

目的分析1例肥厚性心肌病(HCM)病儿临床表现、基因突变结果及临床意义。方法 1例10月龄的病儿,因咳嗽、发热、呼吸困难及反复发绀而入院。首诊为Ⅰ型呼吸衰竭、心功能不全与重症肺炎。超声心动图、心脏计算机断层扫描、心脏磁共振成像扫描以及心电图检查诊断为HCM。病儿及父母行全基因组测序,检测基因突变情况。结果据测序分析,发现病儿携带一种新的杂合突变体RAF1c.770C>T,但其父母未发现相同突变体。RAF1突变可能导致具有HCM特征的NOONAN和LEOPARD综合征,但结合病儿临床表现及相关检查,排除了这2种综合征的可能性。结论首次报道了一种单独的突变体RAF1c.770C>T,具有该突变体的病儿有HCM的特征,但发病极早,婴儿期即出现明显的心肌肥厚,临床表现极为严重。因此,应对携带该突变点的HCM病儿家族成员进行长期追踪随访。

Objective To investigate the clinical manifestations and gene mutations of an infant with hypertrophic cardiomyopathy （HCM） and related clinical significance. Methods An infant aged 10 months was admitted due to cough, pyrexia, dyspnea, and recurrent cyanosis. The initial diagnoses were type Ⅰ respiratory failure, cardiac insufficiency, and severe pneumonia. The infant was diagnosed with HCM based on the results of echocardiography, cardiac computed tomography scan, cardiac magnetic resonance imaging, and electrocardiography. Whole genome sequencing was performed for the infant and the parents to detect gene mutation. Results The results of sequencing showed a novel heterozygous mutation, RAF1 c.770C〉T, in the infant, which was not observed in the parents. RAF1 mutation may cause NOOAAN syndrome and LEOPARD syndrome with the features of HCM, but based on the infant’s clinical manifestations and the results of related examinations, these two syndromes were excluded. Conclusion A single mutant of RAF1 c.770C〉T is reported for the first time. Infants with this mutation have the features of HCM and develop this disease at an extremely young age, with marked myocardial hypertrophy in infancy and severe clinical manifestations. Therefore, the family members of infants with HCM who carry this mutation should be followed up for a long time.