BACKGROUND: Inactivating mutations of the SLC12A3 gene are the most common cause of Gitelman's syndrome (GS), a disorder inherited as an autosomal recessive trait. In a minority of cases, GS-like phenotypes are caused by mutations in the CLCNKB gene. METHODS: We searched for SLC12A3 and CLCNKB gene mutations in 13 Chinese patients (9 males and 4 females, age 35 +/- 14 years) from 8 unrelated families with the clinical and biochemical features of GS. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. RESULTS: We identified 10 mutations distributed throughout the SLC12A3 gene. Seven are novel variants, including 4 missense mutations (Gly196Val, Cys430Gly, Gly439Val and Leu571Pro), 2 deletions (1384delG and 346-353delACTGATGG) and 1 in-frame insertion (997insCys). Three mutations were recurrent, including 2 missense mutations (Thr60Met and Asp486Asn) and 1 deletion (2883-2884delAG). The homozygous or heterozygous mutation Thr60Met was found in 8 of 13 patients. There were no mutations detected in the CLCNKB gene. CONCLUSIONS: Thr60Met may be the most common mutation in Chinese patients with GS. Possible specific genotype-phenotype correlations were difficult to identify. Copyright 2008 S. Karger AG, Basel.
BACKGROUND: Inactivating mutations of the SLC12A3 gene are the most common cause of Gitelman's syndrome (GS), a disorder inherited as an autosomal recessive trait. In a minority of cases, GS-like phenotypes are caused by mutations in the CLCNKB gene. METHODS: We searched for SLC12A3 and CLCNKB gene mutations in 13 Chinese patients (9 males and 4 females, age 35 +/- 14 years) from 8 unrelated families with the clinical and biochemical features of GS. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. RESULTS: We identified 10 mutations distributed throughout the SLC12A3 gene. Seven are novel variants, including 4 missense mutations (Gly196Val, Cys430Gly, Gly439Val and Leu571Pro), 2 deletions (1384delG and 346-353delACTGATGG) and 1 in-frame insertion (997insCys). Three mutations were recurrent, including 2 missense mutations (Thr60Met and Asp486Asn) and 1 deletion (2883-2884delAG). The homozygous or heterozygous mutation Thr60Met was found in 8 of 13 patients. There were no mutations detected in the CLCNKB gene. CONCLUSIONS: Thr60Met may be the most common mutation in Chinese patients with GS. Possible specific genotype-phenotype correlations were difficult to identify. Copyright 2008 S. Karger AG, Basel.
Authors: Jinwei Zhang; Keith Siew; Thomas Macartney; Kevin M O'Shaughnessy; Dario R Alessi Journal: Hum Mol Genet Date: 2015-05-20 Impact factor: 6.150
Authors: Ciaran Richardson; Kei Sakamoto; Paola de los Heros; Maria Deak; David G Campbell; Alan R Prescott; Dario R Alessi Journal: J Cell Sci Date: 2011-03-01 Impact factor: 5.285
Authors: Fatema H Rafiqi; Annie Mercier Zuber; Mark Glover; Ciaran Richardson; Stewart Fleming; Sofija Jovanović; Aleksandar Jovanović; Kevin M O'Shaughnessy; Dario R Alessi Journal: EMBO Mol Med Date: 2010-02 Impact factor: 12.137