X-连锁无丙种球蛋白血症BTK基因突变1例并文献复习
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摘要
目的探讨X-连锁无丙种球蛋白血症(X-linked agammaglobulinemia,XLA)BTK基因突变临床及实验室特点,梳理诊断思路和治疗方法以提高临床医师对XLA的认识。方法回顾性分析1例X-连锁无丙种球蛋白血症BTK基因突变患者的临床特征、实验室检查、基因测序及诊治经过,复习相关文献并分析。结果 6岁男性患儿表现为自出生反复呼吸道感染、肺炎、免疫球蛋白减少或缺如,对症治疗加免疫球蛋白静点有效。BTK基因杂合突变:[c.83G>A,p.28R>H],父母热点基因突变验证显示母亲为杂合携带者,父亲不存在相应位点突变。结论本研究患儿XLA是BTK基因杂合突变,丙种球蛋白缺陷所致;在临床表现基础上通过BTK基因分析有助于XLA患儿的进一步明确诊断,且有利于发现携带者和进行遗传咨询。
Objective To discuss X-linked agammaglobulinemia(XLA) with BTK heterozygosis mutations clinical and laboratory characteristics and explore new diagnostic and therapeutic methods, in order to improve the understanding of XLA among clinical physicians. Method The clinical material of one XLA case with BTK mutations were analyzed and related literature were reviewed. Result A 6-year-old boy presented with recurrent infection, pneumonia and lower immunoglobulin. After genetic analyses, the heterozygosis mutations [c.83G>A, p.28R>H] in the BTK gene was found. The result of parent's gene detection proved that her father don't have corresponding locus mutation but her mother is a carrier. Conclusion This case of XLA is a severe immunodeficiency due to BTK mutation. Based on the clinical manifestations, XLA patients can be diagnosed by further genetic analysis of BTK. It is good to find BTK gene carriers and do some genetic consultation.
Objective To discuss X-linked agammaglobulinemia(XLA) with BTK heterozygosis mutations clinical and laboratory characteristics and explore new diagnostic and therapeutic methods, in order to improve the understanding of XLA among clinical physicians. Method The clinical material of one XLA case with BTK mutations were analyzed and related literature were reviewed. Result A 6-year-old boy presented with recurrent infection, pneumonia and lower immunoglobulin. After genetic analyses, the heterozygosis mutations [c.83G>A, p.28R>H] in the BTK gene was found. The result of parent's gene detection proved that her father don't have corresponding locus mutation but her mother is a carrier. Conclusion This case of XLA is a severe immunodeficiency due to BTK mutation. Based on the clinical manifestations, XLA patients can be diagnosed by further genetic analysis of BTK. It is good to find BTK gene carriers and do some genetic consultation.
引文
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[16]王悦.常染色体隐性遗传的无丙种球蛋白血症[J].国外医学分册,2005,32(6):372-374.
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[18]王会贞,卫海燕,陈永兴.X连锁无丙种球蛋白血症1例临床表现及基因检测[J].中国实用医药,2014,9(16):36-37.
[19]邓朝晖,蒋丽蓉,张斌,等.抗体缺陷病并发肝硬化一例并文献复习[J].中华儿科杂志,2016,54(5):379-382.
[2]García García E,Staines Boone AT,Vargas Hernández A,et al.Clinical and mutational features of X-linked agammaglobulinemia in Mexico[J].Clinical Immunology,2016(165):38-44.
[3]Yang L,Wu EY,Tarrant TK,et al.Immune gamma globulin therapeutic indications in immune deficiency and autoimmunity[J].Curr Allergy Asthma Rep,2016,16(8):55.
[4]Lindvall JM,Blomberg KE,Voliaho J,et al.Bruton’s tyrosine kinase:cell biology,sequence conservation,mution spectrum,si RNA modifications,and expression profiling[J].Immunol Rev,2005(203):200-215.
[5]陶英博,陈慧珊,曾华松.X-连锁无丙种球蛋白血症BTK基因新发突变1例报告[J].中华临床免疫和变态反应杂志,2013,7(2):203-205.
[6]Corneth OB,Klein Wolterink RG,Hendriks RW.BTK signaling in B cell differentiation and autoimmunity[J].Curr Top Microbiol Immunol,2016(393):67-105.
[7]Conley ME,Mathias D,Treadaway J,et al.Mutation in btk in patients with presumed X-linked agammaglobuline-mia[J].Am J Hum Genet,1998,62(5):1034-1043.
[8]Sigmon JR,Kasasbeh E,Krishnaswamy G.X-linked agammaglobulinemia diagnosed late in life:case report and review of the literature[J].Clin Molr Allergy,2008,6(5):5.
[9]Conley ME,Broides A,Hernandez-Trujillo V,et al.Genetic analysis of patients with defects in early B-cell development[J].Immunol Rev,2005(203):216-234.
[10]张晓敏,李红,李强,等.六例X连锁无丙种球蛋白血症患儿BTK基因突变检测及临床分析[J].中华遗传学杂志,2014,31(1):29-33.
[11]王莹,应文静,孙金峤,等.中国X连锁无丙种球蛋白血症40例基因型表型相关性分析[J].中国循证儿科杂志,2012,7(1):4-10.
[12]吴静,张慧,龚若兰,等.8例非Bruton酪氨酸激酶基因突变无丙种球蛋白血症患儿临床特征和基因突变/多态性分析[J].发育医学电子杂志,2015,3(4):232-236.
[13]黄菲,朱海静,周湘.Bruton酪氨酸激酶BTK及其抑制剂的研究进展[J].中国医科大学学报,2014,45(6):617-624.
[14]Chopra N,Wales TE,Joseph RE.Dynamic allostery mediated by a conserved tryptophan in the tec family kinases[J].PLo S Comput Biol,2016,12(3):24.
[15]孔祥东,莫桂玲,刘宁,等.X-连锁无丙种球蛋白血症家系BTK基因突变分析及产前诊断研究[J].中华医学杂志,2014,94(18):1405-1408.
[16]王悦.常染色体隐性遗传的无丙种球蛋白血症[J].国外医学分册,2005,32(6):372-374.
[17]Quartier P,DebréM,De Blic J,et al.Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia:a retrospective survey of 31 patients[J].J Pediatr,1999,134(5):589.
[18]王会贞,卫海燕,陈永兴.X连锁无丙种球蛋白血症1例临床表现及基因检测[J].中国实用医药,2014,9(16):36-37.
[19]邓朝晖,蒋丽蓉,张斌,等.抗体缺陷病并发肝硬化一例并文献复习[J].中华儿科杂志,2016,54(5):379-382.