Genetic Analysis of SLC12A3 Gene in Chinese Patients with Gitelman Syndrome

Abstract

Background The incidence of Gitelman syndrome (GS) has been increasing in our hospital. The aim of this study was to explore the diagnostic accuracy and features of SLC12A3 gene in Chinese patients with GS. Material/Methods We searched the literature about Chinese patients with GS in the PubMed database up to July 2018 and also included 8 GS Chinese patients from our hospital in our analysis that explored the features of SLC12A3 gene. We divided all the patients into 3 groups according to diagnostic consensus. Complete compliance was defined to mean containing 2 allelic mutations, partial compliance to mean one allelic mutation, and clinical compliance to mean no mutations. Results Totally, 137 patients were enrolled in this study and 90 mutations were counted. Missense mutations accounted for over 72% in Chinese GS patients and the most common one was Thr60Met. According to the consensus, there were 102 patients (74.5%) in the complete compliance group, 31 patients (22.6%) in the partial compliance group, and only 4 patients (2.9%) in the clinical compliance group. Conclusions The SLC12A3 gene analysis in Chinese GS patients revealed that the most common mutation was Thr60Met, one of the missense mutations. Most of the patients were in the complete compliance group (i.e., 2 allelic mutations); the other cases might be explained by gene rearrangement.

Phenotypic differences of mutation‐negative cases in Gitelman syndrome clinically diagnosed in adulthood

“…This may be attributed to the small numbers in this study, and additional investigation may be necessary. Compared with studies from other countries that describe mutation hotspots in SLC12A3 in GS patients, neither the p. Thr60Met and p. Asp486Asn mutations, which are the most common in Chinese patients (F. Wang et al, 2017; Zeng et al, 2019), nor the p. Leu859Pro and p. Arg861Cys mutations, which are the most common in French patients (Vargas‐Poussou et al, 2011), were identified. These results suggest that, in different population backgrounds, mutation hotspots are different.…”

Allele-specific RT-PCR for the rapid detection of recurrent SLC12A3 mutations for Gitelman syndrome

“…The meticulous analyses of all reported SLC12A3 mutations to date clearly shows that recurrent mutations in SLC12A3 were relatively common 5,24,[35][36][37] . In Japan, two recurrent mutations (p. R642C and p.L858H) are reportedly responsible for 38.6% of all allelic mutations in GS families 37 .…”

Review and Analysis of Two Gitelman Syndrome Pedigrees Complicated with Proteinuria or Hashimoto’s Thyroiditis Caused by Compound Heterozygous SLC12A3 Mutations

“…Compound heterozygous mutations are more common than homozygous mutations [ 6 ]. Among Chinese GS patients, compound heterozygous mutations accounted for 72.5%, and missense mutations accounted for more than 72% of different mutations in the SLC12A3 gene [ 29 ]. The missense mutation Arg83Gln is more common in the GS pedigree, but the pathogenic mechanism remains unclear [ 30 ].…”

“…The missense mutation Arg83Gln is more common in the GS pedigree, but the pathogenic mechanism remains unclear [ 30 ]. Zeng et al found that among the 137 cases of GS patients in China, six patients carried compound heterozygotes of Arg83Gln, among which two patients also carried three responsible mutation points [ 29 ]. The mutant found in proband A: NC_000016.10:g.56872655_56872667 (gcggacatttttg>accgaaaatttt) is composed of multiple mutations, including NM_001126108.2:c.976delG mutation, which has been confirmed to be pathogenic [ 31 , 32 ].…”

“…Zelikovic et al found that, in addition to SLC12A3 , the R438H mutation of CLCNKB may play a role in the pathogenesis of GS [ 39 ]. Among the 137 GS patients in China, 9 patients were found to carry the Arg904Gln mutation, and therefore, these can be regarded as frequent mutations [ 29 ]. Arg904Gln may be an area for increased research in Chinese GS patients [ 36 ].…”