Clin Nephrol. 2021 Sep;96(3):165-174. doi: 10.5414/CN110425.
As the most frequent inherited tubulopathy, Gitelman syndrome (GS), has an incidence that has increased worldwide. The distribution of gene mutation hotspots deserves exploration. In addition, GS is not a benign syndrome; however, the diagnostic process of GS has not yet been completely detailed.
We report two cases of GS pedigrees involving two previously unreported mutations, c. 676G>A, p. A226T and c. 421G>A, p. G141R, in the gene and reviewed relevant literature. We searched the literature for nucleotide of in PubMed and other databases as of April 20, 2020.
A total of 1,794 detected mutated alleles in 939 patients worldwide were included in this study. Splicing mutations and p. Gly741Arg were mutation hotspots in a European population. P. Leu858His and p. Thr60Met were mutation hotspots in an Asian population. P. Leu858His and p. Thr180Lys were considered mutation hotspots in the Japanese population, while p. Thr60Met and p. Asp486Asn were considered mutation hotspots in the Chinese population.
Our results identified two novel mutation sites (c. 676G>A, p. A226T and c. 421G>A, p. G141R), if their pathogenicity was determined this could contribute to the enrichment of database resources on GS. Our study has compiled the most comprehensive gene mutation database in the world thus far to reveal that different regions have different mutation hotspots in SLC12A3. Moreover, the establishment of a diagnostic process for GS has important implications for confirmed cases.
探讨 Gitelman 综合征（GS）基因热点突变分布情况。方法：报道 2 例 GS 家系，涉及基因 c.676G>A，p.A226T 和 c.421G>A，p.G141R 两个未报道的突变，检索 2020 年 4 月 20 日前 PubMed 及其他数据库中有关的文献，分析全球 939 例患者共 1794 个突变等位基因。结果：共纳入 1794 个突变等位基因，939 例患者。剪接突变和 p.Gly741Arg 是欧洲人群的突变热点，p.Leu858His 和 p.Thr60Met 是亚洲人群的突变热点，p.Leu858His 和 p.Thr180Lys 是日本人群的突变热点，p.Thr60Met 和 p.Asp486Asn 是中国人群的突变热点。结论：本研究报道了基因 c.676G>A，p.A226T 和 c.421G>A，p.G141R 两个新的突变位点，如果确定其致病性，将有助于丰富 GS 数据库资源。本研究对目前全球最大的 SLC12A3 基因突变数据库进行了分析，不同区域的 SLC12A3 基因突变热点不同。建立 GS 的诊断流程对明确诊断具有重要意义。
