Gene Analysis,treatment,and Follow-up Of Sixty Patients With Bart Ter Syndrome

Objective:Bartter syndromes?BS?is a group of rare autosomal-recessive inherite d salt-losing tubulopathies.The aim of this study was to analyze the variants of t he causal genes in 60 Chinese BS patients,to describe their clinical features and t o follow up the treatment results.Methods:In this study,cases were collected from network and hospital visits.Ge ne variation analysis was conducted by second-generation high-throughput sequenci ng,Sanger sequencing validation and multiple ligase prop-dependent amplification?MLPA?technology.The pathogenicity of variants were evaluated,and the characte ristics of variation in each gene were summarized thereupon.According to differen t involved genes,60 children were divided into four groups:BS1,BS2,BS3 and BS4a.The clinical and biochemical data of these patients were collected and retro spectively analyzed to characterize the clinical features of these subtypes.The diffe rences between BS1 and BS3 were statistically analyzed.Children were mainly tre ated with indomethacin and potassium chloride.Examination of height,weight,ser um and urinary biochemical indicators were performed regularly.Possible drug side effects were monitored momentarily.Results:1.In this study,a total of 60 patients with genetically confirmed BS we re collected,including 42 patients with BS3,9 patients with BS1,5 patients with BS2 and 4 patients with BS4a.2.A total of 15 SLC12A1 gene variants were identified in 9 children with BS1,11 of which were newly discovered.A total of 10 KCNJ1 gene variants were ident ified in 5 children with BS2,6 of which were newly discovered variants.A total of 36 CLCNKB gene variants were identified in 42 children with BS3,16 of whic h were newly discovered variants,and the frequency of large fragment deletion m utations?including total gene deletion?was as high as 46/84?55%?.Three BSND gene variants were identified in 4 children with BS4a,one of which was newly di scovered variant.3.Polyuria and growth retardation are the most common clinical manifestations of BS.Children with BS1,BS2 and BS4a usually manifested as antenatal BS,whic h are often characterized by polyhydramnion and premature delivery.BS1 and BS2are often accompanied by increased urinary calcium/creatinine ratio and nephrocal cinosis,of which the proportion of renal calcium deposition in the large groups of BS2 in Israel and Germany was up to 100%.All children with BS4a presented s ensorineural deafness.Mostly presented as classical BS,BS3 is usually born at ful l-term and manifests after birth,but has more tends to electrolyte disturbance.4.With the exception of BS2,most of the patients presented with obvious hypoka lemia,hypochloric alkalosis,elevated renin activity and hyperaldosteronism.In this study,the indicators of 9 patients with BS1 and 42 patients with BS3 were com pared.The gestational weeks and CO₂CP of BS1 were lower than BS3,and the di fferences had significant statistical significance.The proportion of nephrocalcinosis was higher than that of BS3,and the difference had significant statistical significa nce.Renin degree and urinary calcium/urinary creatinine value of BS1 were higher than BS3 with statistical significance.The concentrations of chlorine and magnesi um of BS1 were higher than that of BS3 with statistical significance.5.After more than 3 years of drug treatment and follow-up,most children with B S1-3 showed significant improvement in symptoms of polydipsia,electrolyte disturb ance and growth retardation.The effect of indomethacin on BS4a growth retardatio n is inferior to other subtypes.Conclusions:1.In this study,a total of 64 variations were found in 4 genes rel ated to BS,including 34 new ones,which enriched the Human Gene Mutation Da tabase.2.BS3 may be the subtype with the highest incidence in China,and large deletio ns may be the mutation type with the highest frequency.3.Patients with BS3 are usually born at full-term,but the tendency of electrolyte disturbance in this subtype is more obvious.Patients with BS1 are usually preterm delivery,but the dehydration of BS1 was much more serious than that of BS3.4.The treatment regimen with NSAIDs and potassium chloride as the main patter n and potassium preserving diuretics as the auxiliary had obvious effects on BS1-3patients and partial BS4a patients.