中国9例1型巴特综合征SLC12A1基因突变分析

Mutation analysis of SLC12A1 gene in nine Chinese patients with Bartter syndrome type I

目的本研究收集了来自9个1型巴特综合征（Bartter syndrome type I，BS1）家系的9例患儿，并对其进行SLC12A1基因突变分析和基因型，表型相关性研究。方法通过第二代高通量测序对8例表现为出生前巴特综合征（antenatal BS，aBS）和1例表现为经典型巴特综合征（classica1 BS，cBS）共9例BS1患儿进行基因突变分析，同时进行临床表现及生化特点研究，观察患儿治疗前后的病情变化。结果共确定SLC12A1基因15个突变位点，其中11个新突变位点。9例患儿中，7例为复合杂合突变，2例为纯合突变。全部患儿均表现为多饮多尿（9／9），8例患儿生长迟缓（8／9）。9例患儿均表现为低血氯性代谢性碱中毒、基础肾素活性及醛固酮浓度升高（9／9），7例患儿存在低血钾（7／9）。通过吲哚美辛和／或氯化钾治疗，生化指标可基本恢复正常。结论本研究结果丰富了人类基因突变库，并为中国人群遗传咨询和基因诊断的开展提供有益的借鉴。

Objective To analyze the mutations of SLC12A1 gene in nine Chinese families with Bartter syndrome type I （BS1）, and analyze the relationship between genotype and phenotype. Methods The next generation sequencing was used to detect mutations in nine BS1 patients including eight with antenatal BS （aBS） and one with classical BS （cBS）. Clinical characteristics and biochemical findings at the first admission as well as follow-up were reviewed. Results 15 different mutations of SLC12A1 gene were identified, including 11 novel ones. Among nine probands, seven were compound heterozygotes, two were homozygotes. All patients presented with polydipsia and polyuria, and eight with growth retardation. All patients had lower than-normal serum chloride concentration, metabolic alkalosis, and elevated basal renin activity and aldosterone, and seven had hypokalemia. Through treatment of indomethacin and/or potassium chloride, biochemical indicators could roughly restored normal. Conclusion These findings will enrich the human gene mutation database （HGMD） and provide valuable references to the genetic counseling and diagnosis for Chinese population.