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Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes

Fava, Cristiano LU ; Montagnana, Martina; Nilsson, Lena LU ; Burri, Philippe LU ; Jonsson, Anders; Wanby, Par; Wahrenberg, Hans; Hulthén, Lennart LU ; Aurell, Mattias and Guidi, Gian Cesare, et al. (2007) In DNA Sequence 18(5). p.395-399
Abstract
PURPOSE: Gitelman's syndrome (GS) is an inherited autosomal recessive disorder due to loss of function mutations in the SLC12A3 gene encoding the Na-Cl co-transporter (NCCT), the target of thiazide diuretics. The defective function of the NCCT, which normally is expressed in the apical membrane of the distal convolute tubule in the kidney, leads to mild hypotension, hypokalemia, hyperreninemic hyperaldosteronism, mild metabolic alkalosis, hypomagnesemia and hypocalciuria. Up to now, more than 100 mutations of the SLC12A3 gene have been described in GS patients. METHODS: We have collected 30 patients from Sweden with a clinical diagnosis of GS and undertaken a mutation screening by SSCP and successive sequencing of the 26 exons and intronic... (More)
PURPOSE: Gitelman's syndrome (GS) is an inherited autosomal recessive disorder due to loss of function mutations in the SLC12A3 gene encoding the Na-Cl co-transporter (NCCT), the target of thiazide diuretics. The defective function of the NCCT, which normally is expressed in the apical membrane of the distal convolute tubule in the kidney, leads to mild hypotension, hypokalemia, hyperreninemic hyperaldosteronism, mild metabolic alkalosis, hypomagnesemia and hypocalciuria. Up to now, more than 100 mutations of the SLC12A3 gene have been described in GS patients. METHODS: We have collected 30 patients from Sweden with a clinical diagnosis of GS and undertaken a mutation screening by SSCP and successive sequencing of the 26 exons and intronic boundaries. Both mutations were identified in most (n = 28, 93%) and at least one mutation was identified in all patients. RESULTS: We found 22 different mutations evenly distributed throughout the gene, 11 of which have not been described previously. The new variants include 8 missense mutations (Glu68Lys, His69Asn, Argl45His, Vall53Met, Gly230Asp, Gly342Ala, Val677Leu and Gly867Ser), 1 insertion (c.834_835insG on exon 6) and 2 splice-site mutations (c.2667 + lT>G substitution in splicing donor site after exon 22, c.1569-1G>A substitution in the splicing acceptor site before exon 13). CONCLUSION: In Swedish patients with the clinical features of GS, disease-causing mutations in the SLC12A3 gene were identified in most patients. The spectrum of GS mutations is wide making full mutation screening of the SLC12A3 gene necessary to confirm the diagnosis. (Less)
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publication status
published
subject
keywords
SLC12A3, NCCT, mutations, Gitelman's syndrome, hyperreninemic hyperaldosteronism
in
DNA Sequence
volume
18
issue
5
pages
395 - 399
publisher
Harwood Academic
external identifiers
  • pmid:17654016
  • scopus:34547211510
ISSN
1029-2365
DOI
10.1080/10425170701400456
language
English
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yes
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a097bbaf-a14f-4cad-b7fd-54060450f5a4 (old id 1138278)
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2008-08-19 09:58:56
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2017-01-01 04:42:21
@article{a097bbaf-a14f-4cad-b7fd-54060450f5a4,
  abstract     = {PURPOSE: Gitelman's syndrome (GS) is an inherited autosomal recessive disorder due to loss of function mutations in the SLC12A3 gene encoding the Na-Cl co-transporter (NCCT), the target of thiazide diuretics. The defective function of the NCCT, which normally is expressed in the apical membrane of the distal convolute tubule in the kidney, leads to mild hypotension, hypokalemia, hyperreninemic hyperaldosteronism, mild metabolic alkalosis, hypomagnesemia and hypocalciuria. Up to now, more than 100 mutations of the SLC12A3 gene have been described in GS patients. METHODS: We have collected 30 patients from Sweden with a clinical diagnosis of GS and undertaken a mutation screening by SSCP and successive sequencing of the 26 exons and intronic boundaries. Both mutations were identified in most (n = 28, 93%) and at least one mutation was identified in all patients. RESULTS: We found 22 different mutations evenly distributed throughout the gene, 11 of which have not been described previously. The new variants include 8 missense mutations (Glu68Lys, His69Asn, Argl45His, Vall53Met, Gly230Asp, Gly342Ala, Val677Leu and Gly867Ser), 1 insertion (c.834_835insG on exon 6) and 2 splice-site mutations (c.2667 + lT>G substitution in splicing donor site after exon 22, c.1569-1G>A substitution in the splicing acceptor site before exon 13). CONCLUSION: In Swedish patients with the clinical features of GS, disease-causing mutations in the SLC12A3 gene were identified in most patients. The spectrum of GS mutations is wide making full mutation screening of the SLC12A3 gene necessary to confirm the diagnosis.},
  author       = {Fava, Cristiano and Montagnana, Martina and Nilsson, Lena and Burri, Philippe and Jonsson, Anders and Wanby, Par and Wahrenberg, Hans and Hulthén, Lennart and Aurell, Mattias and Guidi, Gian Cesare and Melander, Olle},
  issn         = {1029-2365},
  keyword      = {SLC12A3,NCCT,mutations,Gitelman's syndrome,hyperreninemic hyperaldosteronism},
  language     = {eng},
  number       = {5},
  pages        = {395--399},
  publisher    = {Harwood Academic},
  series       = {DNA Sequence},
  title        = {Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes},
  url          = {http://dx.doi.org/10.1080/10425170701400456},
  volume       = {18},
  year         = {2007},
}