Clinical utility gene card for: Gitelman syndrome

Knoers, Nine V A M; Devuyst, Olivier; Kamsteeg, Erik‐Jan

doi:10.1038/ejhg.2011.14

Cited by 5 publications

(4 citation statements)

References 15 publications

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“…Because there are GS patients who do not have 2 mutations in SLC12A3 (i.e., a mutation in the noncoding regions or in another gene, which are not included in the test), the clinical sensitivity (proportion of positive tests if the disease is present) is 65% to 80%, depending on the genetic methods used. 7,12,50,[53][54][55] Pathogenic SLC12A3 mutations include larger rearrangements (deletions), which can be picked up by multiplex ligation-dependent probe amplification, 7 and intronic mutations, which can be screened for by cDNA analysis of lymphocytes. 50,56 As genetic testing becomes more accessible and comprehensive, it should be offered to all patients with a clinical suspicion of GS (minimal criteria).…”

Section: Genetic Testingmentioning

confidence: 99%

Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Blanchard

Böckenhauer

Bolignano

et al. 2017

Kidney International

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346

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Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.

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Section: Genetic Testingmentioning

confidence: 99%

Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Blanchard

Böckenhauer

Bolignano

et al. 2017

Kidney International

Self Cite

274

346

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“…GS is a recessively inherited saltlosing tubulopathy with hypokalemic alkalosis, hypomagnesaemia and hypocalciuria. The majority of patients with GS are compound heterozygous for loss-of-function mutations in the SLC12A3 gene that codes for the NCC [28]. A few cases are caused by mutations in the CLCNKB gene that codes for the basolateral ClC-Kb chloride channel in DCT cells [28,29].…”

Section: Pvalb As Candidate Gene In Gitelman Syndromementioning

confidence: 99%

“…The majority of patients with GS are compound heterozygous for loss-of-function mutations in the SLC12A3 gene that codes for the NCC [28]. A few cases are caused by mutations in the CLCNKB gene that codes for the basolateral ClC-Kb chloride channel in DCT cells [28,29]. GS is probably the most common tubulopathy, with a prevalence of heterozygous carrier of an SLC12A3 mutation estimated at 1% in European populations [30].…”

Section: Pvalb As Candidate Gene In Gitelman Syndromementioning

confidence: 99%

Parvalbumin: calcium and magnesium buffering in the distal nephron

Olinger¹,

Schwaller²,

Loffing³

et al. 2012

Nephrology Dialysis Transplantation

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Parvalbumin (PV) is a classical member of the EF-hand protein superfamily that has been described as a Ca(2+) buffer and Ca(2+) transporter/shuttle protein and may also play an additional role in Mg(2+) handling. PV is exclusively expressed in the early part of the distal convoluted tubule in the human and mouse kidneys. Recent studies in Pvalb knockout mice revealed a role of PV in the distal handling of electrolytes: the lack of PV was associated with a mild salt-losing phenotype with secondary aldosteronism, salt craving and stronger bones compared with controls. A link between the Ca(2+)-buffering capacity of PV and the expression of the thiazide-sensitive Na(+)-Cl(-) cotransporter was established, which could be relevant to the regulation of sodium transport in the distal nephron. Variants in the PVALB gene that encodes PV have been described, but their relevance to kidney function has not been established. PV is also considered a reliable marker of chromophobe carcinoma and oncocytoma, two neoplasms deriving from the distal nephron. The putative role of PV in tumour genesis remains to be investigated.

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“…It is characterized by hypopotassic metabolic alkalosis, hypomagnesemia, and hypouricemia [5] . Approximate 140 different mutations in SLC12A3 has been associated to the pathogenesis of GS, including insertion mutations, splicing mutations, and missense mutations [6]. GS can manifest as a variety of clinical symptoms.…”

Section: Discussionmentioning

confidence: 99%

A Case Report: Gitelman Syndrome or Bartter Syndrome?

WU¹,

Hu²,

Wang³

et al. 2020

Preprint

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Background: Gitelman syndrome (GS) is a rare autosomal recessive inherited tubular disease which is caused by mutation in the SLC12A3 gene. It is characterized by hypokalemic alkalosis with hypomagnesemia and hypocalciuria, and can cause serious complications such as arrhythmia, syncope, sudden death, etc. Bartter syndrome (BS) is similar to Gitelman syndrome in clinical and laboratory examinations. If lack of sufficient understanding of the disease, it is easy to cause misdiagnosis and missed diagnosis. Case presentation: A 6-year-old Chinese girl presented with history of hand and foot spasms and was diagnosed with hypokalemia. Although multiple symptomatic treatments of potassium supplementation was given, is the concentration of potassium was still at a low level. Gene analysis revealed that the presence of two heterozygous mutations, i.e. a missense mutation c.248G> A and a frameshift mutation c.2875_2876del, in the SLC12A3 gene.The child was diagnosed with Gitelman syndrome(GS) due to SLC12A3 compound heterozygous mutation. Through treatment, the level of ion metabolism in children remains stable. Conclusions: By reviewing its clinical characteristics and diagnosis and treatment ideas, we can help improve clinicians' understanding of children's GS.

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Clinical utility gene card for: Gitelman syndrome

Cited by 5 publications

References 15 publications

Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Parvalbumin: calcium and magnesium buffering in the distal nephron

A Case Report: Gitelman Syndrome or Bartter Syndrome?

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