Blood pressure in children with renal cysts and diabetes syndrome

Seeman, Tomáš; Weigel, Friederike; Bláhová, Květa; Fencl, Filip; Průhová, Štěpánka; Hermes, Katharina; Klaus, Richard; Lange-Sperandio, Bärbel; Grote, Veit; John-Kroegel, Ulrike

doi:10.1007/s00431-021-04165-1

Cited by 3 publications

(3 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it should be noted that renin–angiotensin–aldosterone system (RAAS) activation is scarce in patients with HNF1β defects, whereas it is a cardinal symptom of Gitelman patients. Moreover, hypertension is present in 22% of children with ADTKD-HNF1β, whereas Gitelman patients are generally hypotensive compared to healthy family members [ 69 , 95 ]. Although it should be noted that chronic kidney disease in ADTKD-HNF1β patients may contribute to the hypertension phenotype.…”

Section: Electrolyte Disturbances In Adtkd-hnf1β Patientsmentioning

confidence: 99%

Mechanisms of ion transport regulation by HNF1β in the kidney: beyond transcriptional regulation of channels and transporters

Tholen

Hoenderop

Baaij

2022

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor essential for the development and function of the kidney. Mutations in and deletions of HNF1β cause autosomal dominant tubule interstitial kidney disease (ADTKD) subtype HNF1β, which is characterized by renal cysts, diabetes, genital tract malformations, and neurodevelopmental disorders. Electrolyte disturbances including hypomagnesemia, hyperuricemia, and hypocalciuria are common in patients with ADTKD-HNF1β. Traditionally, these electrolyte disturbances have been attributed to HNF1β-mediated transcriptional regulation of gene networks involved in ion transport in the distal part of the nephron including FXYD2, CASR, KCNJ16, and FXR. In this review, we propose additional mechanisms that may contribute to the electrolyte disturbances observed in ADTKD-HNF1β patients. Firstly, kidney development is severely affected in Hnf1b-deficient mice. HNF1β is required for nephron segmentation, and the absence of the transcription factor results in rudimentary nephrons lacking mature proximal tubule, loop of Henle, and distal convoluted tubule cluster. In addition, HNF1β is proposed to be important for apical-basolateral polarity and tight junction integrity in the kidney. Interestingly, cilia formation is unaffected by Hnf1b defects in several models, despite the HNF1β-mediated transcriptional regulation of many ciliary genes. To what extent impaired nephron segmentation, apical-basolateral polarity, and cilia function contribute to electrolyte disturbances in HNF1β patients remains elusive. Systematic phenotyping of Hnf1b mouse models and the development of patient-specific kidney organoid models will be essential to advance future HNF1β research.

show abstract

Section: Electrolyte Disturbances In Adtkd-hnf1β Patientsmentioning

confidence: 99%

Mechanisms of ion transport regulation by HNF1β in the kidney: beyond transcriptional regulation of channels and transporters

Tholen

Hoenderop

Baaij

2022

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

show abstract

“…2 High blood pressure was identified in 22% of children with HNF1B gene abnormalities. 39 Knowledge of the presence of fetal/neonatal gene mutation is critical to guide the need for ongoing follow-up as fetal-onset HNF1B deletion-associated renal parenchymal abnormalities and neonatal reduced renal function may initially resolve in infancy/early childhood, with later development of renal, metabolic and neurodevelopmental abnormalities. 40 Identification of children who may benefit from regular assessment and early assistance with respect to neurodevelopmental or behavioural disorders is important, a prospective cohort study of 223 French school-aged children (mean age 9.6 years) found that 12.7% and 3.6% of children carrying an HNF1B deletion and a disease-associated variant respectively had special educational needs, compared with 1.2% of French children in general.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy outcome with maternal HNF1B gene mutations and 17q12 deletions

Morton

Wilson

2022

Obstet Med

View full text Add to dashboard Cite

There is an increasing body of literature regarding monogenic diabetes, particularly the more common forms of glucokinase and HNF1-alpha mutations (MODY2 and MODY3). There is relatively little published literature regarding rarer mutations. HNF1-beta mutations and 17q12 deletions may be associated with a broad range of organ dysfunction, renal disease and diabetes in particular resulting in high-risk pregnancies. This manuscript describes pregnancy outcomes in a woman with an HNF1-beta mutation and 2 women with an HNF1B/17q12 deletion and reviews the previously published literature. It highlights the significant rate of adverse maternal and fetal outcomes, and the maternal features suggestive of the diagnosis which should be considered in preconception counselling.

show abstract

“…Of note, renin-angiotensin-aldosterone system (RAAS) activation is scarce in patients with HNF1b defects, whereas it is one of the main symptoms of Gitelman syndrome. Moreover, hypertension is present in 22% of children with HNF1b nephropathy [76]. Gitelman patients are generally hypotensive compared with healthy family members, though cases with hypertension in later life have been described [6,77].…”

Section: Hnf1b -Adtkd-hnf1bmentioning

confidence: 99%

The genetic spectrum of Gitelman(-like) syndromes

Schlingmann

Baaij

2022

Current Opinion in Nephrology &Amp; Hypertension

View full text Add to dashboard Cite

Purpose of reviewGitelman 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 findingsDisturbed 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.SummaryAltogether, 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.

show abstract

Blood pressure in children with renal cysts and diabetes syndrome

Cited by 3 publications

References 12 publications

Mechanisms of ion transport regulation by HNF1β in the kidney: beyond transcriptional regulation of channels and transporters

Mechanisms of ion transport regulation by HNF1β in the kidney: beyond transcriptional regulation of channels and transporters

Pregnancy outcome with maternal HNF1B gene mutations and 17q12 deletions

The genetic spectrum of Gitelman(-like) syndromes

Contact Info

Product

Resources

About