Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes
(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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https://lup.lub.lu.se/record/1138278
- author
- organization
- publishing date
- 2007
- type
- Contribution to journal
- 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
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Diabetes and Endocrinology (013241530), Pediatrics/Urology/Gynecology/Endocrinology (013240400), Hypertension and Cardiovascular Disease (013242540)
- id
- a097bbaf-a14f-4cad-b7fd-54060450f5a4 (old id 1138278)
- date added to LUP
- 2016-04-01 11:57:41
- date last changed
- 2024-03-14 02:49:06
@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}}, keywords = {{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}}, doi = {{10.1080/10425170701400456}}, volume = {{18}}, year = {{2007}}, }