Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome
Year: 2002
Type: article
Study design: Observational Study
Abstract: The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G.
Source: Human Mutation
DOI: 10.1002/humu.9045
Institutions: University of Milan, Istituti Clinici di Perfezionamento, Ospedale Pediatrico Giovanni XXIII, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Ospedale San Luigi Gonzaga, Istituti Ospitalieri di Cremona, Arcispedale Sant'Anna, Casa Sollievo della Sofferenza, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Aziende Socio Sanitarie Territoriali di Lecco
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W1978319067