Relationship Between Genotype And Phenotype Of High Mutation In 20 Patients With Gitelman Syndrome

Objective Mutation genotype and phenotype in patients with SLC12A3 gene in 20 cases collected from the Qingdao and Zaozhuang regions of Gitelman syndrome were analyzed and compared,to explore the relationship between the genotype and phenotype of the high mutation.Methods The research group from 2013 to 2016 in the Affiliated Hospital of Qiingdao University hospital and Central Hospital of Zaozhuang Mining Group in 20 patients by gene sequencing confirmed Gitelman syndrome patients.There were 13 male patients and 7 female patients,with an average age of(33±12)years.20 patients were analyzed about Mutant genotype,clinical manifestation,serum potassium,serum magnesium,blood bicarbonate,Plasma angiotensin,aldosterone,24h urinary calcium/creatinine,The mutant genotype was found in 20 patients.The general clinical data and laboratory test results of different genotypes were corresponding analysis and comparison.Gene sequencing was performed in 50 unrelated healthy subjects to find if there were any mutations in the SLC12A3 gene.Statistical analysis was performed by SPPSS13.0 software.Results 20 cases were diagnosed in 14 patients showed limb weakness,4 patients showed tetany,1 patients showed polyuria,nocturia,6 patients had no clinical symptoms,only low blood potassium was found in the examination,5 cases of patients with onset age less than 18 years.All 20 patients had hypokalemia,and 16 patients had hypokalemia,20 patients were more than 27mmol/L blood bicarbonate,All 20 patients had low urinary calcium.Mutations in the SLC12A3 gene were found in 20 patients,A total of 15 related mutations were identified,9 missense mutations(Cys430Gly?Leu571Pro?Thr60Met?Asp486Asn?Glu429Lys?Ala264Gly?Ser283Thr?Thr163Met?Arg913Gln)5 deletion mutation(1384delG?346-353delACTGATGG?2883-2884delAG?1740delC?2877-2878delAG)1 insertion mutations(997insCys),Heterozygous mutations were found in 2 cases,homozygous mutations in 1 cases,and heterozygous heterozygous mutations in 17 cases,8 patients with ala264gly,were homozygous mutation,the mutation rate is about 21.1%(8/3 8),There were only 1 loci mutations in 2 patients(2/20=10%),Much lower than previously reported40%in the literature.50 cases of non health related patients did not detect mutations in SLC12A3.Incidence of ala264gly carriers of limb weakness,foot twitch,and carry the patients with other mutations had no significant difference occurred urinary symptoms,blood potassium,laboratory examination ala264gly carriers of blood serum magnesium,bicarbonate,plasma angiotensin,aldosterone,24h urinary calcium/creatinine in patients with other mutations with no significant difference.Conclusions Phenotype and associated mutations may differ in patients with Gitelman syndrome in different regions.Gitelman syndrome phenotype diversity and heterogeneity are the key factors of genotype and phenotype with more difficult to determine,and patients with Gitelman syndrome phenotype showed multiple mutation interaction results;postnatal diet,gender and environmental impact can not be ignored.At present,there is no direct evidence to support the high risk mutation in this study.ALa264GLy has a clear relationship with phenotype.