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.
Abstract
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.
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