Early Development of Hyperparathyroidism Due to Loss of<i>PTH</i>Transcriptional Repression in Patients With HNF1β Mutations?

Ferrè, Silvia; Bongers, Ernie M.H.F.; Sonneveld, Ramon; Cornelissen, Elisabeth A.M.; Vlag, Johan van der; Boekel, Gerben A.J. van; Wetzels, Jack F.M.; Hoenderop, Joost G. J.; Bindels, René J. M.; Nijenhuis, Tom

doi:10.1210/jc.2012-3453

Cited by 30 publications

(24 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The prevalence of hypomagnesemia ranges from 0 to 100% in the different studies, but the prevalence in adults is consistently higher in those studies that included children and adults. 43,44,49 The same appears to be true with regard to the extrarenal phenotypes of elevated liver enzymes, pancreatic hypoplasia, and diabetes mellitus. These differences might be related to a delayed onset of the phenotypical changes.…”

Section: Epidemiologymentioning

confidence: 80%

“…42 Early Onset Hyperparathyroidism Ferrè et al observed early hyperparathyroidism and parathyroid hormone (PTH) levels that were judged inappropriately high relative to kidney function in several patients with known HNF1B mutations or deletions. 43 HNF1b was demonstrated to be expressed by PTHproducing parathyroid gland cells. 43 Wild-type HNF1b inhibited transcription of the PTH gene, thus functioning as a transcriptional repressor of PTH production.…”

Section: Mental Retardation and Autismmentioning

confidence: 98%

“…43 HNF1b was demonstrated to be expressed by PTHproducing parathyroid gland cells. 43 Wild-type HNF1b inhibited transcription of the PTH gene, thus functioning as a transcriptional repressor of PTH production. HNF1b mutations found in patients lost their repressive effects on PTH transcription, which could explain early onset hyperparathyroidism in patients with HNF1B mutations.…”

Section: Mental Retardation and Autismmentioning

confidence: 98%

See 2 more Smart Citations

Hepatocyte Nuclear Factor 1β–Associated Kidney Disease

Verhave

Bech

Wetzels

et al. 2016

Journal of the American Society of Nephrology

Self Cite

130

121

View full text Add to dashboard Cite

Hepatocyte nuclear factor 1b (HNF1b)-associated disease is a recently recognized clinical entity with a variable multisystem phenotype. Early reports described an association between HNF1B mutations and maturity-onset diabetes of the young. These patients often presented with renal cysts and renal function decline that preceded the diabetes, hence it was initially referred to as renal cysts and diabetes syndrome. However, it is now evident that many more symptoms occur, and diabetes and renal cysts are not always present. The multisystem phenotype is probably attributable to functional promiscuity of the HNF1b transcription factor, involved in the development of the kidney, urogenital tract, pancreas, liver, brain, and parathyroid gland. Nephrologists might diagnose HNF1b-associated kidney disease in patients referred with a suspected diagnosis of autosomal dominant polycystic kidney disease, medullary cystic kidney disease, diabetic nephropathy, or CKD of unknown cause. Associated renal or extrarenal symptoms should alert the nephrologist to HNF1b-associated kidney disease. A considerable proportion of these patients display hypomagnesemia, which sometimes mimics Gitelman syndrome. Other signs include early onset diabetes, gout and hyperparathyroidism, elevated liver enzymes, and congenital anomalies of the urogenital tract. Because many cases of this disease are probably undiagnosed, this review emphasizes the clinical manifestations of HNF1b-associated disease for the nephrologist.

show abstract

Section: Epidemiologymentioning

confidence: 80%

Section: Mental Retardation and Autismmentioning

confidence: 98%

Section: Mental Retardation and Autismmentioning

confidence: 98%

See 1 more Smart Citation

Hepatocyte Nuclear Factor 1β–Associated Kidney Disease

Verhave

Bech

Wetzels

et al. 2016

Journal of the American Society of Nephrology

Self Cite

130

121

View full text Add to dashboard Cite

show abstract

“…In a recent report of a single-centre cohort of ten HNF1B mutation carriers with available parathyroid hormone (PTH) plasma levels, seven had CKD stage <3 [glomerular filtration rate (GFR)>60 ml/min/1.73 m 2 based on either estimated or measured creatinine clearances], yet elevated PTH levels (6.6-16.3 pmol/l, normal <6.5) [52]. One of these patients had a diagnosis of primary hyperparathyroidism with parathyroidectomy at age 23 years, several years before the HNF1B mutation was identified.…”

Section: Primary Hyperparathyroidismmentioning

confidence: 99%

“…One of these patients had a diagnosis of primary hyperparathyroidism with parathyroidectomy at age 23 years, several years before the HNF1B mutation was identified. The group subsequently identified an HNF1B-responsive element in the PTH promoter and demonstrated repression of PTH transcription by HNF1B [52]. The elevated PTH levels were made more remarkable by the fact that six of these seven patients had concomitant hypomagnesaemia (0.41-0.64 mmol/l): hypomagnesaemia is usually associated with hypoparathyroidism, as magnesium is an important cofactor for the calcium-sensing receptor to initiate PTH release [53].…”

Section: Primary Hyperparathyroidismmentioning

confidence: 99%

HNF1B-associated clinical phenotypes: the kidney and beyond

2015

View full text Add to dashboard Cite

Mutations in HNF1B, the gene encoding hepatocyte nuclear factor 1β are the most commonly identified genetic cause of renal malformations. HNF1B was first identified as a disease gene for diabetes (MODY5) in 1997, and its involvement in renal disease was subsequently noted through clinical observations in pedigrees affected by MODY5. Since then, a whole spectrum of associated phenotypes have been reported, including genital malformations, autism, epilepsy, gout, hypomagnesaemia, primary hyperparathyroidism, liver and intestinal abnormalities and a rare form of kidney cancer. The most commonly identified mutation, in approximately 50 % of patients, is an entire gene deletion occurring in the context of a 17q12 chromosomal microdeletion that also includes several other genes. Some of the associated phenotypes, especially the neurologic ones, appear to occur only in the context of this microdeletion and thus may not be directly linked to HNF1B. Here we review the spectrum of associated phenotypes and discuss potential implications for clinical management.

show abstract

PTH and Vitamin D

Khundmiri

Murray

Lederer

2016

Comprehensive Physiology

225

158

View full text Add to dashboard Cite

PTH and Vitamin D are two major regulators of mineral metabolism. They play critical roles in the maintenance of calcium and phosphate homeostasis as well as the development and maintenance of bone health. PTH and Vitamin D form a tightly controlled feedback cycle, PTH being a major stimulator of vitamin D synthesis in the kidney while vitamin D exerts negative feedback on PTH secretion. The major function of PTH and major physiologic regulator is circulating ionized calcium. The effects of PTH on gut, kidney, and bone serve to maintain serum calcium within a tight range. PTH has a reciprocal effect on phosphate metabolism. In contrast, vitamin D has a stimulatory effect on both calcium and phosphate homeostasis, playing a key role in providing adequate mineral for normal bone formation. Both hormones act in concert with the more recently discovered FGF23 and klotho, hormones involved predominantly in phosphate metabolism, which also participate in this closely knit feedback circuit. Of great interest are recent studies demonstrating effects of both PTH and vitamin D on the cardiovascular system. Hyperparathyroidism and vitamin D deficiency have been implicated in a variety of cardiovascular disorders including hypertension, atherosclerosis, vascular calcification, and kidney failure. Both hormones have direct effects on the endothelium, heart, and other vascular structures. How these effects of PTH and vitamin D interface with the regulation of bone formation are the subject of intense investigation.

show abstract

Early Development of Hyperparathyroidism Due to Loss ofPTHTranscriptional Repression in Patients With HNF1β Mutations?

Abstract: Our data demonstrate that HNF1β is a novel repressor of human PTH gene transcription, which could contribute to the development of hyperparathyroidism in patients with HNF1β mutations or deletions.

Cited by 30 publications

References 38 publications

Hepatocyte Nuclear Factor 1β–Associated Kidney Disease

Hepatocyte Nuclear Factor 1β–Associated Kidney Disease

HNF1B-associated clinical phenotypes: the kidney and beyond

PTH and Vitamin D

Contact Info

Product

Resources

About