Fen Wang1, Chuan Shi1, Yunying Cui1, Chunyan Li1, Anli Tong2. 1. Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China. 2. Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China. tonganli@hotmail.com.
Abstract
BACKGROUND: Gitelman syndrome (GS) is a rare autosomal recessive disease caused by loss-of-function mutations in the SLC12A3 gene, and is characterized by hypokalemia and metabolic alkalosis. In this study, we aimed to study the genotype, phenotype, and treatment in 42 GS patients, the largest sample size so far in mainland China. METHOD: We retrospectively studied the clinical data and genetic characteristics of 42 patients diagnosed with GS in Peking Union Medical College Hospital from 2012 to 2015. Therapeutic efficacy of spironolactone and potassium supplements was also studied retrospectively. RESULTS: Eighty-one mutation alleles were found in 42 patients, and total of 52 distinctly different mutation alleles were identified, of which 15 were new mutation alleles. p.Asp486Asn was a hotspot in our series, with the allele frequency being 19.7 % (16/81), and was found in 13 patients (31.0 %). Treatment with spironolactone or potassium supplements alone significantly increased serum potassium concentration by 0.36 ± 0.37 and 0.45 ± 0.35 mmol/l, respectively (both P < 0.05), and combined therapy with spironolactone and potassium increased serum potassium concentration by 0.69 ± 0.64 mmol/l (P < 0.05). CONCLUSIONS: 18.5 % (15/81) mutation sites identified in 42 Chinese GS patients are novel. p.Asp486Asn mutation is a hotspot, which is different from the reports from other countries. Spironolactone could moderately elevate serum potassium level, and spironolactone in combination with potassium supplements tended to be more effective.
BACKGROUND:Gitelman syndrome (GS) is a rare autosomal recessive disease caused by loss-of-function mutations in the SLC12A3 gene, and is characterized by hypokalemia and metabolic alkalosis. In this study, we aimed to study the genotype, phenotype, and treatment in 42 GSpatients, the largest sample size so far in mainland China. METHOD: We retrospectively studied the clinical data and genetic characteristics of 42 patients diagnosed with GS in Peking Union Medical College Hospital from 2012 to 2015. Therapeutic efficacy of spironolactone and potassium supplements was also studied retrospectively. RESULTS: Eighty-one mutation alleles were found in 42 patients, and total of 52 distinctly different mutation alleles were identified, of which 15 were new mutation alleles. p.Asp486Asn was a hotspot in our series, with the allele frequency being 19.7 % (16/81), and was found in 13 patients (31.0 %). Treatment with spironolactone or potassium supplements alone significantly increased serum potassium concentration by 0.36 ± 0.37 and 0.45 ± 0.35 mmol/l, respectively (both P < 0.05), and combined therapy with spironolactone and potassium increased serum potassium concentration by 0.69 ± 0.64 mmol/l (P < 0.05). CONCLUSIONS: 18.5 % (15/81) mutation sites identified in 42 Chinese GSpatients are novel. p.Asp486Asn mutation is a hotspot, which is different from the reports from other countries. Spironolactone could moderately elevate serum potassium level, and spironolactone in combination with potassium supplements tended to be more effective.
Authors: A Bettinelli; M G Bianchetti; E Girardin; A Caringella; M Cecconi; A C Appiani; L Pavanello; R Gastaldi; C Isimbaldi; G Lama Journal: J Pediatr Date: 1992-01 Impact factor: 4.406
Authors: Weizhen Ji; Jia Nee Foo; Brian J O'Roak; Hongyu Zhao; Martin G Larson; David B Simon; Christopher Newton-Cheh; Matthew W State; Daniel Levy; Richard P Lifton Journal: Nat Genet Date: 2008-04-06 Impact factor: 38.330
Authors: Goncalo R Abecasis; Adam Auton; Lisa D Brooks; Mark A DePristo; Richard M Durbin; Robert E Handsaker; Hyun Min Kang; Gabor T Marth; Gil A McVean Journal: Nature Date: 2012-11-01 Impact factor: 49.962