摘要
目的:探讨反复发热伴MEFV基因突变患儿基因型与临床表型关系以及MEFV基因突变在反复发热患儿诊治中的价值。方法:报道3例反复发热患儿经全外基因检测发现伴MEFV基因突变,并对3例患儿临床表现、实验室相关检查及MEFV基因突变位点进行分析。结果:3例患儿均反复发热。病例1,发热间歇期不固定(1~6 d)、发热时伴腹痛、头晕等非特异性症状,多次实验室检查不支持感染性、风湿免疫性及肿瘤相关性疾病,抗感染、非甾体类抗炎药及激素治疗无效。病例2,发热间歇期4周,发热时外周血白细胞总数及中性粒细胞数升高,C反应蛋白(CRP)升高,热退后上述指标恢复正常,生长发育不受影响,多次诊断“化脓性扁桃体炎”。病例3,间歇期为2~8周,实验室检查同病例2,多次诊断“化脓性扁桃体炎”及“扁桃体炎”。3例患儿行全外显子组基因检测,结果均检测出伴MEFV基因突变。病例1患者分别杂合携带c.1105(exon3)C>T(p.P369S)和c.1223(exon3)G>A(p.R408Q)突变位点,两个突变均来自母亲,不符合“家族性地中海热(FMF)”遗传学诊断标准,诊断为“发热待查”。病例2患者杂合携带c.1105(exon3)C>T(p.P369S)突变位点,该突变来自父亲,结合临床及家族史,诊断“周期性发热伴阿弗他口炎-咽炎-淋巴结炎综合征(PFAPA)”。病例3患者分别杂合携带c.442(exon2)G>C(p.E148Q)和c.329(exon2)T>C(p.L110P)突变位点,父亲为L110P杂合子,母亲为L110P杂合子及E148Q纯合子,结合临床,亦诊断“PFAPA”。结论:中国人群MEFV多态性位点不是明确致病性位点,因此,对反复发热伴MEFV基因突变患儿检测结果需结合临床表现、家族史及其它情况进行全面分析。
Objective:To investigate the relationship between genotype and clinical phenotype with recur-rent fever accompanied by MEFV gene mutation and the value of MEFV gene mutation in the recur-rent fever diagnosis.Methods:Three cases of recurrent fever with MEFV gene mutation were report-ed by whole exome sequencing(WES),and the clinical manifestations,laboratory tests,and mutation sites of the MEFV gene were analyzed.Results:All three patients presented with recurrent fever,and one patient had an irregular intermittent period of fever(1-6 days)and complained of abdominal pain,dizziness,and other symptoms.Multiple laboratory examinations showed a lack of infection,rheumatism,immunity,and tumor-related indicators,and the anti-infection,non-steroidal anti-inflammatory drugs and hormone therapy were ineffective.The intermittent period of fever in case 2 was 4 weeks,and"suppurative tonsillitis"was diagnosed many times.During fever,the blood cells,neutrophils,and CRP levels increased.After fever,the above indexes returned to normal,and the growth and development were normal.Case 3 had repeated fever with an intermittent period of 2-8 weeks,which was diagnosed several times as"suppurative tonsillitis"and"tonsillitis",and the labora-tory examination and prognosis were the same as case 2.To find the etiology,3 cases were detected with MEFV gene mutation by WES.In case 1,the mutation sites were c.1105(exon3)C>T,P369S and c.1223(exon3)G>A,R408Q.Both mutations came from the mother,who was a heterozygote.It does not meet the genetic diagnostic criteria for familial Mediterranean fever(FMF).In case 2,the mutation site was c.1105(exon3)C>T,P369S.The father was heterozygote and then diagnosed with periodic fever,aphthous,pharyngitis,and adenitis syndrome(PFAPA).In case 3,the mutation sites were C.442(exon2)G>C,E148Q and C.329(exon2)T>C,L110P.The father was heterozygote of L110P,and the mother was heterozygote of L110P and homozygote of E148Q.Case 3 was also diag-nosed with PFAPA.Conclusion:There is no specific relationship between the clinical manifestations and the MEFV gene mutation site.The MEFV gene mutation should be comprehensively analyzed.
作者
武贝
杨琰
詹晓芸
万丽君
谭沛
赵阿兰
芦映红
黄娟
WU Bei;YANG Yan;ZHAN Xiaoyun;WAN Lijun;TAN Pei;ZHAO Alan;LU Yinghong;HUANG Juan(Dept.of Pediatric Hematology,Maternal and Child Hospital of Hubei Province,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430070,Hubei,China)
出处
《武汉大学学报(医学版)》
CAS
2024年第4期485-489,共5页
Medical Journal of Wuhan University