CAJ | 학술논문

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.
목적 묘술Ⅰ형원발성고초산뇨증(PHI)일가계3례동포환자적림상특정병진행치병기인AGXT돌변분석.방법 통과직접측서법분석해가계AGXT기인돌변위점급차요등위기인상태.이100명건강인작위대조.결과 AGXT기인분석발현2개신적착의잡합돌변화1개기왕보도과적돌변:1호외현자제49위단안산돌변위량안산(p.M49L,c.145A＞C),2호외현자제72위천동선알돌변위이량안산(p.N72I,c.215A＞ T),이급10호외현자제333위밀마자적무의잡합돌변(p.R333*).p.M49L화p.R333*균여차요등위기인IVS1+74 bp정순식구형,재중국인군중해차요등위기인형빈솔원고우고가색인.결론 신발현적2개돌변위점가능여PHI유관,단기치병성화분자치병궤제상수진일보연구.저시국내수차대PHI적치병기인분석연구.
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 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.