论文部分内容阅读
目的:分析12例儿童Gitelman综合征(Gitelman syndrome，GS)的临床和实验室检查及n SCL12A3基因变异情况。n 方法:收集GS患儿临床资料，采用全外显组测序技术对患儿致病变异进行筛查，再通过Sanger测序对患儿及其父母进行验证。结果:12例GS患儿的诊断年龄2岁8个月至15岁，男10例、女2例，6例因感染、5例因身材矮小、1例因下肢无力就医时发现血钾降低。12例患儿均检测出n SLC12A3基因变异，其中复合杂合变异11例，纯合变异1例；共检测出19个致病等位基因，15个错义变异，2个移码变异，2个剪切区域变异。发现未报道的新变异位点3个，分别为c.578_582dupCCACC(p.Asn195Profs*109)、c.251C>T(p.Pro84Leu)、c.2843G>A(p.Trp948X)。n 结论:儿童GS临床症状不典型，以年长儿多见，对偶然发现的低钾血症伴身材矮小或偏矮患儿，应注意GS的筛查。绝大多数GS患儿存在n SLC12A3基因2个致病变异，以复合杂合变异为主，以p.Thr60Met最为常见。新变异的发现丰富了n SLC12A3基因变异谱。n “,”Objective:To summarize clinical manifestations and results of genetic testing in 12 children with Gitelman syndrome (GS).Methods:Clinical data of the children was collected. Whole exome sequencing(WES) was carried out to screen potential variants of genomic DNA. Candidate variants were verified by Sanger sequencing.Results:The patients have included 10 boys and 2 girls, whom were diagnosed at between 2.8 to 15.0 year old. Six patients were due to infections, 5 were due to short stature, and 1 was due to lower limb weakness. All patients were found to carry variants of n SLC12A3 gene, which included 11 with compound heterozygous variants and 1 with homozygous variant. All of the 19 alleles of the n SLC12A3 gene carried by the patients were delineated, which included 15 missense variants, 2 frameshift variants and 2 splice region variants.These variants were unreported previously, which included c. 578_582dupCCACC(p.Asn195Profs*109), c.251C>T(p.Pro84Leu) and c. 2843G>A(p.Trp948X).n Conclusion:The clinical symptoms of GS in children are atypical and often seen in older children. For children with occasional hypokalemia associated with growth failure, GS should be suspected. The majority of GS children carry two pathogenic variants of the n SLC12A3 gene, mainly compound heterozygotes, among which p. Thr60Met is the most common one. The discovery of new variants has enriched the spectrum of n SLC12A3 gene variants.n