i型原发性高草酸尿症一家系agxt基因突变分析 - 中华肾脏病杂志.pdf

中华肾脏病杂志2014 年6 月第30 卷第6 期 Chin J Nephrol, June 2014, Vol. 30, No.6 ·413 · ·临床研究 · I 型原发性高草酸尿症一家系 AGXT基因突变分析 高延霞 王晓慧 郎艳华 周占宇 刘军 王艳 邵乐平 【摘要】 目的 描述I 型原发性高草酸尿症（PHI ）一家系3 例同胞患者的临床特征并进行 致病基因AGXT突变分析。方法 通过直接测序法分析该家系AGXT基因突变位点及次要等 位基因状态。以100 名健康人作为对照。结果 AGXT基因分析发现2 个新的错义杂合突变 和1 个既往报道过的突变：1 号外显子第49 位蛋氨酸突变为亮氨酸（p.M49L ，c.145A ＞C ），2 号 外显子第72 位天冬酰胺突变为异亮氨酸（p.N72I ，c.215A ＞T ），以及10 号外显子第333 位密码 子的无义杂合突变（p.R333* ）。p.M49L 和p.R333*均与次要等位基因IVS1+74 bp 呈顺式构型， 在中国人群中该次要等位基因型频率远高于高加索人。结论 新发现的2 个突变位点可能与 PHI 有关，但其致病性和分子致病机制尚需进一步研究。这是国内首次对PHI 的致病基因分析 研究。 【关键词】 高草酸尿症，原发性； 系谱； 突变； AGXT 基因 AnalysisofAGXT genemutationinaprimaryhyperoxaluriatypeIfamily GaoYanxia*, Wang Xiaohui,LangYanhua,ZhouZhanyu,LiuJun,WangYan,ShaoLeping.*DepartmentofNephrology, AffiliatedHospital,SchoolofMedicine,QingdaoUniversity,Qingdao 266003,China Correspondingauthor:ShaoLeping,Email:lepingshao@163.com 【Abstract】 Objective To describe the clinical characteristics, and to analyze the AGXT gene mutation in three siblings with primary hyperoxaluria type I (PHI). Methods AGXT gene mutation was analyzed by direct sequencing analysis in this family, and the minor allele status was also tested. One hundred unrelated healthy subjects were also analyzed as controls. Results Three mutations in AGXT were identified in each of three patients including two novel heterozygous missense mutations and one previously reported variant. One mutation was a methionine to leucine substitution at position 49 (p. M49L, c.145A ＞C) in exon 1, one was an asparagine to isoleucine transition at codon 72 (p.N72I, c.215A ＞T) in exon 2, and another was a heterozygous nonsense mutation at codon 333 (p.R333*). Both p.M49L and p.R333* occured in cis configuration with the minor allele IVS1+ 74 bp. Conclusions Two novel mutations are identified pro