Relationship between genotype and phenotype of high mutation in 20 patients with gitelman syndrome

Objective To analyze the mutation genotype and phenotype of pathogenic gene SLC12A3 in 20 patients with Gitelman syndrome collected from Zaozhuang, and investigate the relationship between genotype and phenotype of the high mutation. Methods The enrolled included 20 patients with Gitelman syndrome confirmed by gene sequencing from 2013 to 2016 in the Affiliated Hospital of Qingdao University and Central Hospital of Zaozhuang Mining Group. There were 13 males and 7 females, with an average age of (33±12) years. The mutant genotype, clinical manifestation, serum potassium, serum magnesium, blood bicarbonate, plasma angiotensin, aldosterone, and 24h urinary calcium/creatinine were analyzed in 20 patients. The mutant genotype was found in 20 patients. The general clinical data and laboratory test results of different genotypes were correspondingly analyzed and compared. Gene sequencing was performed on 50 unrelated healthy subjects to find if there were any mutations in the SLCl2A3 gene.Results Mutations in the SLCl2A3 gene were found in 20 patients. A total of 15 related mutations were identified, including 9 missense mutations (Cys430Gly, Leu571Pro, Thr60Met, Asp486Asn, Glu429Lys, Ala264Gly, Ser283Thr, Thr163Met, Arg913Gln), 5 deletion mutations (1384delG, 346-353delACTGATGG, 2883-2884delAG, 1740delC, 2877-2878delAG), 1 insertion mutation (997insCys). Heterozygous mutations were found in 2 cases, homozygous mutations in 1 case, and heterozygous heterozygous mutations in 17 cases. The Ala264gly mutation was found in 8 cases, and the incidence was 20.5%. There was no significant difference in the clinical manifestations between Ala264Gly carriers and patients with other mutations. There was no significant difference in serum potassium, serum magnesium, blood bicarbonate, plasma angiotensin, aldosterone, and 24-h urinary calcium/creatinine between Ala264Gly carriers and patients with other mutations. Conclusions The Ala264Gly mutation may be a high frequency mutation in two regions of this study. The clinical phenotype caused by high incidence mutation Ala264Gly was not specific.