Spectrum of HNF1B Mutations in a Large Cohort of Patients Who Harbor Renal Diseases

Heidet, Laurence; Decramer, Stéphane; Pawtowski, Audrey; Morinière, Vincent; Bandı́n, Isabel; Knebelmann, Bertrand; Lèbre, Anne-Sophie; Faguer, Stanislas; Guigonis, Vincent; Antignac, Corinne; Salomon, Rémi

doi:10.2215/cjn.06810909

Cited by 252 publications

(295 citation statements)

References 18 publications

Supporting

Mentioning

261

Contrasting

Unclassified

Order By: Relevance

“…7 In addition, although the phenotype within the family appears largely conserved in patients 3 and 5, the literature suggests that in general there is only a limited genotype-phenotype correlation. 8 Environmental factors or epigenetic regulation of HNF1b expression by microRNA could contribute to the above findings.…”

Section: Heterogenic Presentation Of the Multisystem Phenotype Of Hnfmentioning

confidence: 99%

“…16 In a retrospective study of 377 patients with HNF1b mutations, no correlation was found between the type and location of the genetic mutation and severity of kidney failure. 8 …”

Section: Hnf1b-associated Kidney Diseasementioning

confidence: 99%

“…For instance, a recent Belgian study found a 10% prevalence of HNF1B mutations in 205 patients with CAKUT, 44 and similar cohorts yielded prevalence rates of 5%-31%. 6,8,45 In a large cohort of 419 children with CKD, 3 patients showed a mutation in the HNF1B gene. 46 Other studies noted a prevalence of 9% in kidney transplant recipients with unknown primary disease (mostly CAKUT) and up to 40% in patients with the combination of renal malformations and diabetes.…”

Section: Epidemiologymentioning

confidence: 99%

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

125

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: Heterogenic Presentation Of the Multisystem Phenotype Of Hnfmentioning

confidence: 99%

“…16 In a retrospective study of 377 patients with HNF1b mutations, no correlation was found between the type and location of the genetic mutation and severity of kidney failure. 8 …”

Section: Hnf1b-associated Kidney Diseasementioning

confidence: 99%

Section: Epidemiologymentioning

confidence: 99%

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

125

121

View full text Add to dashboard Cite

show abstract

“…Bidirectional sequencing was carried out using a Big Dye Terminator kit (Applied Biosystem, Foster City). Additionally, screening for large rearrangements in HNF1B gene was performed using quantitative multiplex PCR amplification (15,20). The nomenclature for the description of sequence variants was as recommended in www.hgvs.org (last modified May 06, 2009).…”

Section: Dna Mutational Analysismentioning

confidence: 99%

Phenotype and Outcome in Hereditary Tubulointerstitial Nephritis Secondary to UMOD Mutations

Bollée¹,

Dahan²,

Flamant³

et al. 2011

Clinical Journal of the American Society of Nephrology

Self Cite

112

134

View full text Add to dashboard Cite

SummaryBackground UMOD mutations cause familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are nonspecific.Design, setting, participants, & measurements We reviewed cases of UMOD mutations diagnosed in the genetic laboratories of Necker Hospital (Paris, France) and of Université Catholique de Louvain (Brussels, Belgium). We also analyzed patients with MCKD/FJHN but no UMOD mutation. To determine thresholds for hyperuricemia and uric-acid excretion fraction (UAEF) according to GFR, these parameters were analyzed in 1097 patients with various renal diseases and renal function levels.Results Thirty-seven distinct UMOD mutations were found in 109 patients from 45 families, all in exon 4 or 5 except for three novel mutations in exon 8. Median renal survival was 54 years. The type of mutation had a modest effect on renal survival, and intrafamilial variability was high. Detailed data available in 70 patients showed renal cysts in 24 (34.3%) of nonspecific localization in most patients. Uricemia was Ͼ75th percentile in 31 (71.4%) of 42 patients not under dialysis or allopurinol therapy. UAEF (n ϭ 27) was Ͻ75th percentile in 70.4%. Among 136 probands with MCKD/FJHN phenotype, UMOD mutation was found in 24 (17.8%). Phenotype was not accurately predictive of UMOD mutation. Six probands had HNF1B mutations.Conclusions Hyperuricemia disproportionate to renal function represents the hallmark of renal disease caused by UMOD mutation. Renal survival is highly variable in patients with UMOD mutation. Our data also add novel insights into the interpretation of uricemia and UAEF in patients with chronic kidney diseases.

show abstract

“…genotype-phenotype correlation studies have shown that usually individuals with large deletions of the gene develop a milder phenotype, compared to individuals with other types of mutation with total loss of protein function. (35,36,37,38) The second mutational event (M2) is represented by mitotic recombination (50%) 16, nondisjunctions, with or without duplication (about 40%), microscopic and submicroscopic deletions, point mutations, and inactivation of the gene (10%). The second mutation occurs more frequently than the first 94, and is more sensitive to environmental factors, especially those that determine chromosomal rearrangements, such as ionizing radiation.…”

Section: Discussion:-mentioning

confidence: 99%

Congenital Anomalies of the Kidney and Urinary Tract Neoplasms and in the Elderly.

G¹,

Cataldo.²

2017

IJAR

View full text Add to dashboard Cite

Introduction: Congenital abnormalities of the kidneys and urinary tract represented a spectrum of malformations often grouped under the acronym for CAKUT. Normal development of the kidneys and urinary tract is the result of the precise interaction, spatially and temporally coordinated, between two structures, the metanephric mesenchyme (which originates from the nephrogenic cord) and the ureteric bud (which originates from nefrico duct or Wolff). Any alteration, it's genetic, environmental, or stochastic, which influence this process can result in kidney malformations and streets urinariedel present study is to evaluate in relation to clinical attention the incidence of risk in neoplastic 'association cancer and malformation. in adults Materials end Methods: Male patient of 75 suffering from gross hematuria and hernia inquinale sn accompanied by dysuria symptoms, in heavy smoker instrumental ultrasound examination of the urinary tract showed a solid lesion in the posterolateral wall sn aggittante in the bladder lumen The uro-CT examination showed a " abnormality of the urinary tract development with ectopia crusade and merger of the two kidneys located alongside sn (fot, 3.4) of the renal pelvis are addressed before the district complete with double ureteral sn .In at the urethral meatus will highlight a focal thickening protruding into the lumen wall to finely irregular margins, with enhancement after contrast medium. (photo 5.6) the CT examination conducted in the chest (photo 7) confirmed the marked signs of emphysema, the anterior segment of the left upper lobe, in close relationship with bronchus and vessels segmented solid training in margins lobed (29x20 mm axial diameter approximately). At PET-CT accumulation of the tracer in the upper field of the left lung in the paramedian attributable to non-specific reactive process . Fig (8.9), then he performed genetic test that confirmed mutations in the PAX2 Results: The UroCT is the imaging examination with greater sensitivity and specificity. The limit lies in the poor ability to detect flat lesions non-invasive muscle. The urography has been almost entirely supplanted by UroTC. The current biomarkers do not have a sensitivity and specificity greater than urinary cytology, and The aromatic amines, NAT2 and NAT1 of tobacco smoking products, are considered the

show abstract

Spectrum of HNF1B Mutations in a Large Cohort of Patients Who Harbor Renal Diseases

Cited by 252 publications

References 18 publications

Hepatocyte Nuclear Factor 1β–Associated Kidney Disease

Hepatocyte Nuclear Factor 1β–Associated Kidney Disease

Phenotype and Outcome in Hereditary Tubulointerstitial Nephritis Secondary to UMOD Mutations

Congenital Anomalies of the Kidney and Urinary Tract Neoplasms and in the Elderly.

Contact Info

Product

Resources

About