1例家族性地中海热患儿临床特征及基因突变分析
|
摘要
目的探讨家族性地中海热(FMF)的临床特征及基因突变情况。方法选择该院收治的1例间断发热4+年的患儿(年龄13岁)。对该患儿进行全面的体格检查,检测C反应蛋白(CRP)、红细胞沉降率等非特异性炎性指标,筛查致病基因MEFV突变情况,并根据临床诊断进行相应治疗。结果患儿的临床表现符合针对儿童的FMF诊断标准,靶向捕获二代测序证实该患儿MEFV基因存在复合杂合突变,分别为c.442G>C(p.E148Q)和c.1588-69G>A,两个突变分别遗传自父母。给予秋水仙碱治疗后,随访7个月,患儿未再发热,红细胞沉降率降至正常。结论 FMF临床表现包括不定期反复发热,可自行缓解。通过基因突变和秋水仙碱治疗情况可以帮助诊断。
Objective To investigate the clinical features and gene mutations of familial Mediterranean fever(FMF).Methods A 13-year-old child who had intermittent fever for 4+years was treated in our hospital.The child underwent a comprehensive physical examination to detect non-specific inflammatory indicators such as C-reactive protein(CRP)and erythrocyte sedimentation rate.At the same time,the mutation of the disease-causing gene MEFV in this child was screened and then the child was treated according to the clinical diagnosis.Results The clinical manifestations of this child were consistent with the diagnostic criteria for FMF in children.Targeted capture second-generation sequencing confirmed the presence of complex heterozygous mutations in the MEFV gene,c.442 G>C(p.E148 Q)and c.1588-69 G>A,respectively.These two mutations were inherited from the parents.The child was given colchicine treatment and the follow-up of 7 months showed that the child did not have fever and the erythrocyte sedimentation rate was normal.Conclusion The clinical manifestations of FMF include irregular recurrent fever,which could be relieved by itself.Gene mutations and colchicine therapy might help diagnose.
Objective To investigate the clinical features and gene mutations of familial Mediterranean fever(FMF).Methods A 13-year-old child who had intermittent fever for 4+years was treated in our hospital.The child underwent a comprehensive physical examination to detect non-specific inflammatory indicators such as C-reactive protein(CRP)and erythrocyte sedimentation rate.At the same time,the mutation of the disease-causing gene MEFV in this child was screened and then the child was treated according to the clinical diagnosis.Results The clinical manifestations of this child were consistent with the diagnostic criteria for FMF in children.Targeted capture second-generation sequencing confirmed the presence of complex heterozygous mutations in the MEFV gene,c.442 G>C(p.E148 Q)and c.1588-69 G>A,respectively.These two mutations were inherited from the parents.The child was given colchicine treatment and the follow-up of 7 months showed that the child did not have fever and the erythrocyte sedimentation rate was normal.Conclusion The clinical manifestations of FMF include irregular recurrent fever,which could be relieved by itself.Gene mutations and colchicine therapy might help diagnose.
引文
[1] MEJTOUTE T,SAYEL H,ELAKHAL J,et al.The detection of a novel insertion mutation in exon 2of the MEFV gene associated with familial Mediterranean fever in a moroccan family[J].Hum Genome Var,2017(4):17023.
[2] YONG H P,WOOD G,KASTNER D L,et al.Pyrin inflammasome activation and RHOA signaling in the auto inflammatory diseases FMF and HIDS[J].Nature Immunol,2016,17(8):914-921.
[3]沈敏,唐琳,李健,等.中国汉族成人起病家族性地中海热三例[J].中华临床免疫和变态反应杂志,2016,10(1):75-79.
[4] ALGHAMDI M.Familial mediterranean fever,review of the literature[J].Clin Rheumatol,2017,36(1):1-7.
[5]李冀,孙之星,王薇,等.秋水仙碱治疗儿童家族性地中海热12例分析[J].中国实用儿科杂志,2017,32(7):522-525.
[6] SHINOZAKI K,AGEMATSU K,YASUI K,et al.Familial Mediterranean fever in 2Japanese families[J].J Rheumatol,2002,29(6):1324-1325.
[7] KALLINICH T,ORAK B,WITTKOWSKI H.Role of genetics in familial Mediterranean fever[J].Rheumatol,2017,76(4):1-8.
[8] MORADIAN M M,MORADIAN M M,BABIKYAN D,et al.Comprehensive analysis of mutations in the MEFV gene reveal that the location and not the substitution type determines symptom severity inFMF[J].Mol Genet Genomic Med,2017,5(6):742-750.
[9] BEHESHTIAN M,IZADI N,KRIEGSHAUSER G,et al.Prevalence of common MEFV mutations and carrier frequencies in a large cohort of Iranian populations[J].J Genet,2016,95(3):667-674.
[10]CEKIN N,AKYUREK M E,PINARBASI E,et al.MEFV mutations and their relation to major clinical symptoms of familial mediterranean fever[J].Gene,2017(626):9-13.
[11]MIGITA K,IZUMI Y,JIUCHI Y,et al.Familial Mediterranean fever is no longer a rare disease in Japan[J].Arthritis Res Ther,2016,18(1):175-185.
[12]AVI LIVNEH M D,PNINA LANGEVITZ M D,DEBORAH ZEMER M D,et al.Criteria for the diagnosis of familial Mediterranean fever[J].Arthritis Rheum-US,2014,40(10):1879-1885.
[13]KONDI A,HENTGEN V,PIRAM M,et al.Validation of the new paediatric criteria for the diagnosis of familial Mediterranean fever:data from a mixed population of 100children from the French reference centre for auto-inflammatory disorders[J].Rheumatology,2010,49(11):2200-2203.
[14]MEHMET TUNCA M D.Familial Mediterranean fever diagnostic criteria:comment on the article by Livneh et al[J].Arthritis Rheum-US,2010,41(8):1516-1517.
[15]YALCINKAYA F,OZEN S,OZAKAR Z B,et al.A new set of criteria for the diagnosis of familial mediterranean fever in childhood[J].Rheumatology,2009,48(4):395-398.
[16]桂雅迪,帅宗文.成人家族性地中海热一例[J].中华内科杂志,2015,54(10):878-880.
[17]李冀,张岩,王薇,等.误诊为幼年型特发性关节炎的儿童家族性地中海热三例[J].中华儿科杂志,2017,55(5):383-387.
[18]刘鑫,李玥,张智旸,等.成人起病的家族性地中海热一例[J].协和医学杂志,2017,8(22):316-320.
[19]乔巧华,方力争,沈凯,等.家族性地中海热1例报道及文献复习[J].全科医学临床与教育,2014,12(3):349-350.
[20]杨晓萍,朱云杰.家族性地中海热患者一例的护理体会[J].解放军护理杂志,2012,29(9):51-52.
[21]周若雯,马雄,陈萦晅,等.中国成人家族性地中海热1例[J].胃肠病学,2012,17(6):381-383.
[22]韩丽芳,蔡军伟,颜亮,等.中国人群MEFV基因多态性研究[J].实用医学杂志,2006,22(11):1234-1235.
[23]XU H,YANG J,GAO W,et al.Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome[J].Nature,2014,513(7517):237-241.
[24]GAO W,YANG J,LIU W,et al.Site-specific phosphorylation and microtubule dynamics control Pyrin inflammasome activation[J].Proc Natl Acad Sci USA,2016,113(33):4857-4866.
[25]OZEN S,DEMIRKAYA E,ERER B,et al.EULAR recommendations for the management of familial Mediterranean fever[J].Ann Rheum Dis,2016,75(4):644-651.
[2] YONG H P,WOOD G,KASTNER D L,et al.Pyrin inflammasome activation and RHOA signaling in the auto inflammatory diseases FMF and HIDS[J].Nature Immunol,2016,17(8):914-921.
[3]沈敏,唐琳,李健,等.中国汉族成人起病家族性地中海热三例[J].中华临床免疫和变态反应杂志,2016,10(1):75-79.
[4] ALGHAMDI M.Familial mediterranean fever,review of the literature[J].Clin Rheumatol,2017,36(1):1-7.
[5]李冀,孙之星,王薇,等.秋水仙碱治疗儿童家族性地中海热12例分析[J].中国实用儿科杂志,2017,32(7):522-525.
[6] SHINOZAKI K,AGEMATSU K,YASUI K,et al.Familial Mediterranean fever in 2Japanese families[J].J Rheumatol,2002,29(6):1324-1325.
[7] KALLINICH T,ORAK B,WITTKOWSKI H.Role of genetics in familial Mediterranean fever[J].Rheumatol,2017,76(4):1-8.
[8] MORADIAN M M,MORADIAN M M,BABIKYAN D,et al.Comprehensive analysis of mutations in the MEFV gene reveal that the location and not the substitution type determines symptom severity inFMF[J].Mol Genet Genomic Med,2017,5(6):742-750.
[9] BEHESHTIAN M,IZADI N,KRIEGSHAUSER G,et al.Prevalence of common MEFV mutations and carrier frequencies in a large cohort of Iranian populations[J].J Genet,2016,95(3):667-674.
[10]CEKIN N,AKYUREK M E,PINARBASI E,et al.MEFV mutations and their relation to major clinical symptoms of familial mediterranean fever[J].Gene,2017(626):9-13.
[11]MIGITA K,IZUMI Y,JIUCHI Y,et al.Familial Mediterranean fever is no longer a rare disease in Japan[J].Arthritis Res Ther,2016,18(1):175-185.
[12]AVI LIVNEH M D,PNINA LANGEVITZ M D,DEBORAH ZEMER M D,et al.Criteria for the diagnosis of familial Mediterranean fever[J].Arthritis Rheum-US,2014,40(10):1879-1885.
[13]KONDI A,HENTGEN V,PIRAM M,et al.Validation of the new paediatric criteria for the diagnosis of familial Mediterranean fever:data from a mixed population of 100children from the French reference centre for auto-inflammatory disorders[J].Rheumatology,2010,49(11):2200-2203.
[14]MEHMET TUNCA M D.Familial Mediterranean fever diagnostic criteria:comment on the article by Livneh et al[J].Arthritis Rheum-US,2010,41(8):1516-1517.
[15]YALCINKAYA F,OZEN S,OZAKAR Z B,et al.A new set of criteria for the diagnosis of familial mediterranean fever in childhood[J].Rheumatology,2009,48(4):395-398.
[16]桂雅迪,帅宗文.成人家族性地中海热一例[J].中华内科杂志,2015,54(10):878-880.
[17]李冀,张岩,王薇,等.误诊为幼年型特发性关节炎的儿童家族性地中海热三例[J].中华儿科杂志,2017,55(5):383-387.
[18]刘鑫,李玥,张智旸,等.成人起病的家族性地中海热一例[J].协和医学杂志,2017,8(22):316-320.
[19]乔巧华,方力争,沈凯,等.家族性地中海热1例报道及文献复习[J].全科医学临床与教育,2014,12(3):349-350.
[20]杨晓萍,朱云杰.家族性地中海热患者一例的护理体会[J].解放军护理杂志,2012,29(9):51-52.
[21]周若雯,马雄,陈萦晅,等.中国成人家族性地中海热1例[J].胃肠病学,2012,17(6):381-383.
[22]韩丽芳,蔡军伟,颜亮,等.中国人群MEFV基因多态性研究[J].实用医学杂志,2006,22(11):1234-1235.
[23]XU H,YANG J,GAO W,et al.Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome[J].Nature,2014,513(7517):237-241.
[24]GAO W,YANG J,LIU W,et al.Site-specific phosphorylation and microtubule dynamics control Pyrin inflammasome activation[J].Proc Natl Acad Sci USA,2016,113(33):4857-4866.
[25]OZEN S,DEMIRKAYA E,ERER B,et al.EULAR recommendations for the management of familial Mediterranean fever[J].Ann Rheum Dis,2016,75(4):644-651.