常染色体显性遗传性远端肾小管酸中毒一家系SLC4A1基因突变分析

Analysis of SLC4Al gene mutation in an autosomal dominant distal renal tubular acidosis family

目的 研究肾小管酸中毒（RTA）一家系的遗传方式和临床特征及分析致病基因SLC4A1突变情况.方法 通过家系涮查和检测肾小管酸化功能,研究分析遗传特点和肾小管缺陷的定位.通过直接测序法分析SLC4A1基因.100例健康正常人作为对照.结果 该家系共有6例患者确诊为远端肾小管酸中毒（dRTA）,6例均有严重的临床表型（发育障碍、肾脏钙质沉着和肾功能不全）;遗传特点符合常染色体显性遗传.SLC4A1基因分析发现位于20号外显子的一个新突变位点（c.2713dupG,band 3 Qingdao）,该突变导致第905位密码子起始的移码突变（p.Aspg05Glyfs15）.结论 常染色体显性遗传性dRTA可表现严重的临床表型.1个新的SLC4A1突变位点被确定与显性遗传性dRTA有关.这是国内首次对遗传性RTA的报道.

Objective To elucidate the inheritance and clinical characteristics, and to analyze the SLC4Al gene mutation in a family with autosomal dominant distal renal tubular acidosis （dRTA）. Methods Family investigation and renal tubular acidification examination were performed. SLC4Al gene mutation was analyzed by direct sequencing analysis in this family. One hundred unrelated healthy subjects were also analyzed as controls. Results Six patients were diagnosed as autosomal dominant dRTA with severe phenotype in this family. All the patients were heterozygous for a novel 1-bp duplication in exon 20 of SLC4Al （c.2713dupG, band 3 Qingdao）. This duplication resulted in a reading frame for 15 extra condons （instead of 8） before the new stop condon at position 919 （p.Asp905Glyfs15）. Conclusions A novel mutation is identified in association with autosomal dominant dRTA with severe phenotype. This is the first report of hereditary dRTA in China.