I型原发性高草酸尿症一家系AGXT基因突变分析

Analysis of AGXT gene mutation in a primary hyperoxaluria type I family

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＋74bp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。

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, e.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 probably in association with PHI, however their pathogenicity and potential molecular mechanisms should be explored by further investigations. This is the first investigation on mutant gene analysis of PHI in China.