Founder Mutation p.C421F in SLC12A3 Underlies the High Prevalence of Gitelman Syndrome in the Yi Population of China

Background Gitelman syndrome (GS) is an autosomal recessive inherited renal tubular disorder, primarily caused by mutations in the SLC12A3 gene. Its prevalence varies significantly among different populations. Previous studies have found that the incidence rate in the Yunnan Yi community of China is notably higher. Factors such as the founder effect contribute to the unique genetic characteristics observed in isolated populations. This study aims to explore the genetic basis for the increased prevalence of GS in the Yi population, focusing on identifying common mutations in the SLC12A3 gene. Preliminary results suggest that the p.C421F variant may be a founder mutation in this population, which could enhance diagnostic strategies and inform public health initiatives. Methods All patients underwent WES, followed by family analysis and verification with Sanger sequencing.Sanger sequencing was used to detect the p.C421F mutation in 1,000 random volunteers from the Yi population. Haplotype analysis was conducted using PLINK software. Results The prevalence of GS in this region is approximately 1 in 1,000, with an allele frequency of 3% for the p.C421F mutation. All 19 GS patients were homozygous for the p.C421F mutation, and a common haplotype surrounding the p.C421F allele was identified in 17 of the GS patients, with a length of at least 499 kb. Conclusions Our study reports a higher prevalence of GS in the Yunnan Yi community and confirms that this phenomenon is due to the founder effect of the SLC12A3 gene p.C421F mutation.