title: Analysis of mutations of two Gitelman syndrome family SLC12A3 genes and proposed treatments using Chinese medicine.
abstract: OBJECTIVE
  To determine the gene location of two Gitelman syndrome (GS) family SLC12A3 genes and explore treatments using Chinese medicine (CM) prescriptions.
  
  
  METHODS
  In order to locate the two GS mutations, samples were collected from 11 people from two different pedigrees for direct genetic sequencing and comparison of the 26 exons of SLC12A3. Furthermore, the change of serum potassium was monitored throughout the therapy and those two probands undertook a sequential superposition of Western medicine (including potassium, Panangin and potassium-sparing diuretics) with CM prescription based on Buyang Huanwu Decoction () and Sijunzi Decoction (). The treatment included three stages, oral potassium chloride for the first 2 weeks (stage 1), potassium-sparing diuretic and Panangin with potassium chloride for the next 2 weeks (stage 2), CM along with the medicine in stage 2 for the final 2 weeks (stage 3).
  
  
  RESULTS
  The three mutations occurring in proband 1 from pedigree I were Thr60Met, 965-1_976del13ins12 (small indels mutation) and Ala122Ala (homozygous silent mutation). Likewise, three mutations, Asn359Lys, Thr382Met and Arg913Gln, appeared in the proband 2 from pedigree II. The serum potassium levels increasing from baseline to sequential stages were 1.63 mmol/L (baseline), 2.5 mmol/L (stage 1), 3.1 mmol/L (stage 2) and 3.9 mmol/L (stage 3) in the proband 1, and 2.8 mmol/L (baseline), 3.1 mmol/L (stage 1), 3.5 mmol/L (stage 2) and 4.3 mmol/L (stage 3) in the proband 2, respectively. The symptoms (numbness of limbs, weakness, palpitations, etc.) of both probands were all alleviated.
  
  
  CONCLUSIONS
  The mutations of both GS pedigrees can be defined as compound heterozygous mutations, most of which are known as missense mutations. Applying CM could be an appropriate choice for future intervention of GS.
authors.affiliation: Department of Traditional Chinese Medicine, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, China.
authors.forename: Jie-Wei
authors.initials: JW
authors.lastname: Luo
authors.affiliation: Department of Traditional Chinese Medicine, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Meng
authors.affiliation: Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Endocrine and Kidney, Fujian Provincial Hospital, Fuzhou, 350001, China.
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Liang
authors.affiliation: Department of Endocrine and Kidney, Fujian Provincial Hospital, Fuzhou, 350001, China.
authors.forename: Fu-Yuan
authors.initials: FY
authors.lastname: Hong
authors.affiliation: Department of Traditional Chinese Medicine, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, China.
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Zheng
authors.affiliation: Department of Surgical Oncology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350001, China. docluo@126.com.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Li
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D053579:Gitelman Syndrome / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics
chemical_list: C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3
keywords: Chinese medicine; Gitelman syndrome; SLC12A3 gene; mutation
references.citation: Am J Chin Med. 2009;37(1):181-94
references.pmid: 19222121
references.citation: Am J Chin Med. 1991;19(2):155-61
references.pmid: 1816727
references.citation: Am J Reprod Immunol. 1998 Mar;39(3):217-22
references.pmid: 9526611
references.citation: Int J Mol Sci. 2012;13(8):10257-67
references.pmid: 22949859
references.citation: Vet Clin Pathol. 2012 Dec;41(4):455-70
references.pmid: 23130944
references.citation: Eur J Hum Genet. 2012 Mar;20(3):263-70
references.pmid: 22009145
references.citation: Nat Genet. 1996 Jan;12(1):24-30
references.pmid: 8528245
references.citation: Chin Med J (Engl). 1999 Dec;112(12):1068-72
references.pmid: 11721440
references.citation: Methods Find Exp Clin Pharmacol. 2000 Dec;22(10):725-30
references.pmid: 11346892
references.citation: J Vet Sci. 2010 Mar;11(1):43-50
references.pmid: 20195064
references.citation: J Clin Invest. 1998 Apr 15;101(8):1661-9
references.pmid: 9541496
references.citation: J Ethnopharmacol. 2012 Dec 18;144(3):567-75
references.pmid: 23036809
references.citation: Orphanet J Rare Dis. 2008 Jul 30;3:22
references.pmid: 18667063
references.citation: Hypertension. 2000 Sep;36(3):389-94
references.pmid: 10988270
references.citation: J Med Food. 2012 Oct;15(10):863-72
references.pmid: 23039111
references.citation: Am J Physiol Renal Physiol. 2005 Nov;289(5):F989-97
references.pmid: 15985651
references.citation: Nephrology (Carlton). 2009 Feb;14(1):52-8
references.pmid: 19207868
references.citation: Biochem Pharmacol. 1996 Feb 9;51(3):339-43
references.pmid: 8573201
references.citation: Eur J Endocrinol. 2011 Oct;165(4):665-73
references.pmid: 21753071
references.citation: Chem Pharm Bull (Tokyo). 1979 Dec;27(12):2954-8
references.pmid: 540333
references.citation: Nephrol Dial Transplant. 2004 Jul;19(7):1761-6
references.pmid: 15069170
references.citation: Trans Assoc Am Physicians. 1966;79:221-35
references.pmid: 5929460
references.citation: Am J Nephrol. 2008;28(6):900-7
references.pmid: 18580052