Dataset Information

The genetic spectrum of Gitelman(-like) syndromes.

ABSTRACT:

Purpose of review

Gitelman syndrome is a recessive salt-wasting disorder characterized by hypomagnesemia, hypokalemia, metabolic alkalosis and hypocalciuria. The majority of patients are explained by mutations and deletions in the SLC12A3 gene, encoding the Na+-Cl--co-transporter (NCC). Recently, additional genetic causes of Gitelman-like syndromes have been identified that should be considered in genetic screening. This review aims to provide a comprehensive overview of the clinical, genetic and mechanistic aspects of Gitelman(-like) syndromes.

Recent findings

Disturbed Na+ reabsorption in the distal convoluted tubule (DCT) is associated with hypomagnesemia and hypokalemic alkalosis. In Gitelman syndrome, loss-of-function mutations in SLC12A3 cause impaired NCC-mediated Na+ reabsorption. In addition, patients with mutations in CLCKNB, KCNJ10, FXYD2 or HNF1B may present with a similar phenotype, as these mutations indirectly reduce NCC activity. Furthermore, genetic investigations of patients with Na+-wasting tubulopathy have resulted in the identification of pathogenic variants in MT-TI, MT-TF, KCNJ16 and ATP1A1. These novel findings highlight the importance of cell metabolism and basolateral membrane potential for Na+ reabsorption in the DCT.

Summary

Altogether, these findings extend the genetic spectrum of Gitelman-like electrolyte alterations. Genetic testing of patients with hypomagnesemia and hypokalemia should cover a panel of genes involved in Gitelman-like syndromes, including the mitochondrial genome.

SUBMITTER: Schlingmann KP

PROVIDER: S-EPMC9415222 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

The genetic spectrum of Gitelman(-like) syndromes.

Schlingmann Karl P KP de Baaij Jeroen H F JHF

Current opinion in nephrology and hypertension 20220711 5

<h4>Purpose of review</h4>Gitelman syndrome is a recessive salt-wasting disorder characterized by hypomagnesemia, hypokalemia, metabolic alkalosis and hypocalciuria. The majority of patients are explained by mutations and deletions in the SLC12A3 gene, encoding the Na+-Cl--co-transporter (NCC). Recently, additional genetic causes of Gitelman-like syndromes have been identified that should be considered in genetic screening. This review aims to provide a comprehensive overview of the clinical, ge ...[more]

PMID: 35894287

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Dataset Information

The genetic spectrum of Gitelman(-like) syndromes.

Purpose of review

Recent findings

Summary

Publications

The genetic spectrum of Gitelman(-like) syndromes.

Similar Datasets

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