目的 研究两个原发性远端肾小管酸中毒（dRTA）家系的临床特征和致病基因SLC4A1突变情况。方法 通过家系调查、病史采集和生化指标检测，分析dRTA临床表型和遗传特点。通过直接测序法检测SLC4AI基因突变。结果 两个家系共有3例患者（其中两例为母子）确诊为dRTA，均有显著的临床特征，包括身材矮小、代谢性酸中毒、碱性尿、低钾血症和肾脏钙盐沉积。SLC4A1基因分析证实3例患者均存在致病性错义突变R589H（c.1766G > A）。家系1的患儿为SCL4A1的新生突变，家系2患儿的SLC4A1基因突变遗传自其母，符合常染色体显性遗传特点。结论 本研究首次在国内报道遗传性dRTA家系中SLC4A1基因R589H突变。对疑似遗传性dRTA患者进行基因检测可提高早期诊治率。
Abstract
Objective To study the clinical features of two families with distal renal tubular acidosis (dRTA) and mutations in the pathogenic gene SLC4A1. Methods Family investigation, medical history collection, and measurement of biochemical parameters were performed to analyze the clinical phenotype and genetic characteristics of dRTA. Direct sequencing was used to detect SLC4A1 gene mutations. Results Three patients in these two families (two of them were mother and son) were diagnosed with dRTA with typical clinical features, including short stature, metabolic acidosis, alkaline urine, hypokalemia, and nephrocalcinosis. SLC4A1 gene analysis showed that all the three patients had a pathogenic missense mutation R589H (c.1766G > A). The child in family 1 had a de novo mutation of SLC4A1, and the child in family 2 had an SLC4A1 gene mutation inherited from the mother, which met the characteristic of autosomal dominant inheritance. Conclusions This study reports the R589H mutation in SLC4A1 gene in families with hereditary dRTA for the first time in China. Clinical physicians should perform gene detection for patients suspected of hereditary dRTA to improve the diagnosis and treatment of this disease.
关键词
肾小管酸中毒 /
常染色体显性遗传 /
SLC4A1 /
家系研究
Key words
Renal tubular acidosis /
Autosomal dominant inheritance /
SCL4A1 /
Family investigation
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参考文献
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基金
国家自然科学基金（81471088；81670714）。
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