ArticleClinical journal of the American Society of Nephrology : CJASN2011
Recurrent deep intronic mutations in the SLC12A3 gene responsible for Gitelman's syndrome.
Article in Clinical journal of the American Society of Nephrology : CJASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 66 citations in OpenAlex.
- Revisiting the Genetics of Hypophosphatasia.Journal of inherited metabolic disease · 2025Review
- A novel homozygous SLC12A3 mutation causing Gitelman syndrome with co-existent autoimmune thyroiditis: a case report and review of the literature.CEN case reports · 2024Review
- Novel Intronic Mutations of theInternational journal of general medicine · 2023Article
- Clinical and genetic approach to renal hypomagnesemia.Biomedical journal · 2022Review
- The Contribution ofFrontiers in medicine · 2022Review
- Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Bartter and Gitelman Syndromes: A Primer for Clinicians.International journal of molecular sciences · 2021Review
- Allele-specific RT-PCR for the rapid detection of recurrent SLC12A3 mutations for Gitelman syndrome.NPJ genomic medicine · 2021Article
- Urinary Extracellular Vesicles for Renal Tubular Transporters Expression in Patients With Gitelman Syndrome.Frontiers in medicine · 2021Article
- Analysis of Pathogenic Pseudoexons Reveals Novel Mechanisms Driving Cryptic Splicing.Frontiers in genetics · 2021Article
- Clinical and Genetic Features in 31 Serial Chinese Children With Gitelman Syndrome.Frontiers in pediatrics · 2021Article
- Clinical Genetic Screening in Adult Patients with Kidney Disease.Clinical journal of the American Society of Nephrology : CJASN · 2020Review
- Type 2 diabetes mellitus caused by Gitelman syndrome-related hypokalemia: A case report.Medicine · 2020Article
- Review
- Intronic CNVs and gene expression variation in human populations.PLoS genetics · 2019Article
- Genomic medicine for kidney disease.Nature reviews. Nephrology · 2018Review
- Deep intronic mutations and human disease.Human genetics · 2017Review
- Hypokalemia, hypomagnesemia, hypocalciuria, and recurrent tetany: Gitelman syndrome in a Chinese pedigree and literature review.Clinical case reports · 2017Article
- Inherited and acquired disorders of magnesium homeostasis.Current opinion in pediatrics · 2017Review
- Mutation profile and treatment of Gitelman syndrome in Chinese patients.Clinical and experimental nephrology · 2017Article
- Cryptic exon activation in SLC12A3 in Gitelman syndrome.Journal of human genetics · 2017Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesGitelman's syndrome (GS) is an autosomal recessive renal tubular disorder caused by mutations in the SLC12A3 gene encoding the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC). Despite meticulous sequencing of genomic DNA, approximately one-third of GS patients are negative or heterozygotes for the known mutations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Because blood leukocytes express NCC mRNA, we evaluate whether deep intronic mutations contribute to GS patients with uniallelic or undetectable SLC12A3 mutations. Twenty-nine patients with GS (men/women = 16/13), including eight negative and 21 uniallelic SLC12A3 mutations from 19 unrelated families, and normal controls were enrolled in an academic medical center. Analysis of cDNA from blood leukocytes, sequencing of the corresponding introns of genomic DNA for abnormal transcript, and analysis of NCC protein expression from renal biopsy were performed.
resultsWe identified nine Taiwan aboriginal patients carrying c.1670-191C→T mutations in intron 13 and 10 nonaboriginal patients carrying c.2548+253C→T mutations in intron 21 from 14 families (14/19). These two mutations undetected in 100 healthy subjects created pseudoexons containing new premature termination codons. Haplotype analysis with markers flanking SLC12A3 revealed that both mutations did not have founder effects. Apical NCC expression in the DCT of renal tissue was markedly diminished in two patients carrying deep intronic mutations.
conclusionsDeep intronic mutations in SLC12A3 causing defective NCC expression can be identified with the RNA-based approach in patients with GS. c.1670-191C→T and c.2548+253C→T are hot spot mutations that can be screened in GS patients with uniallelic or negative SLC12A3 mutations.
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