Large Kidney Cysts in HNF1B Nephropathy Mimicking Autosomal Dominant Polycystic Kidney Disease.

Rationale: Hepatocyte nuclear factor 1 beta (HNF1B) nephropathy is a rare autosomal dominant monogenic kidney disease. We present a case mimicking autosomal dominant polycystic kidney disease (ADPKD), highlighting the phenotypic heterogeneity of HNF1B-related disease. Presenting concerns of the patient: A 37-year-old man presented with hypertensive urgency, accompanied by flank pain and abdominal distension. Despite the absence of familial kidney disease, imaging revealed large bilateral kidney cysts resembling ADPKD. Diagnosis: We initially suspected de novo ADPKD. However, negative genetic testing results for PKD1 and PKD2 led to a 43-gene cystic kidney sequencing panel which identified a deletion encompassing the entire HNF1B gene. Intervention: To alleviate discomfort caused by the kidney cysts, ultrasound-guided aspiration and foam sclerotherapy were performed. Tolvaptan, used for treating high-risk ADPKD, was not prescribed after confirming the diagnosis was HNF1B nephropathy. Outcomes: A diagnosis of HNF1B nephropathy was reached following gene panel testing. Abdominal symptoms improved following cyst aspiration and foam sclerotherapy. Novel findings: HNF1B nephropathy has a variable presentation but can lead to cysts appearing like ADPKD. A 43-gene cystic kidney sequencing panel identified the diagnosis in this uncertain case.

Justification: La néphropathie associée à HNF1B est une maladie rénale monogénique autosomique dominante rare. Nous présentons un cas s'étant présenté comme une polykystose rénale autosomique dominante (ADPKD), ce qui met en évidence l'hétérogénéité phénotypique de la néphropathie associée à HNF1B. Présentation du cas: Un homme de 37 ans présentant une crise hypertensive accompagnée de douleurs au flanc et d'une distension abdominale. Malgré l'absence d'antécédents familiaux de néphropathie, l'imagerie a révélé de gros kystes rénaux bilatéraux ressemblant à l'ADPKD. Diagnostic: Nous avons initialement suspecté une ADPKD de novo. Cependant, les résultats négatifs aux tests génétiques pour PKD1 et PKD2 ont conduit à un panel de séquençage de 43 gènes de rein kystique qui a permis d'identifier une délétion englobant l'ensemble du gène HNF1B. Intervention: Une aspiration et une sclérothérapie à la mousse guidées par échographie ont été effectuées pour soulager l'inconfort causé par les kystes rénaux. Le tolvaptan, qui est utilisé pour traiter le risque élevé de progression de l'ADPKD, n'a pas été prescrit après la confirmation du diagnostic de néphropathie associée à HNF1B. Résultats: Un diagnostic de néphropathie à HNF1B a été posé à la suite du test de panel de gènes. Les symptômes abdominaux se sont améliorés après l'aspiration des kystes et l'échosclérothérapie à la mousse. Nouveaux résultats: La néphropathie associée à HNF1B a une présentation variable, mais peut conduire à l'apparition de kystes comme l'ADPKD. Un panel de séquençage de 43 gènes de rein kystique a confirmé le diagnostic dans ce cas incertain.

Increased Liver Enzymes: An Under-Recognized Finding in Maturity-Onset Diabetes of the Young Type 5 (MODY 5).

Maturity-onset diabetes of the young type 5 (MODY 5) is characterized by a single gene mutation in the HNF1B gene. This frequently leads to insulin resistance and presents as young-onset diabetes. Other manifestations can occur in organs expressing hepatocyte nuclear factor-1 beta. This case report highlights family members with MODY 5 presenting with increased liver enzymes with no etiology. The siblings and their mother had a point mutation p.Arg235Trp in HNF1B gene located at 17q12. This variant is associated with autosomal dominant MODY 5 with renal cysts also known as renal cysts and diabetes syndrome.

Cystic kidney diseases in children.

Cystic kidney disease comprises a broad group of heterogeneous diseases, which differ greatly in age at onset, disease manifestation, systemic involvement, disease progression, and long-term prognosis. As our understanding of these diseases continues to evolve and new treatment strategies continue to emerge, correctly differentiating and diagnosing these diseases becomes increasingly important. In this review, we aim to highlight the key features of the most relevant cystic kidney diseases, underscore important diagnostic characteristics of each disease, and present specific management options if applicable.

Liver Transplantation and Development of Diabetes in an Adolescent Male With HNF1B Disease.

Mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene cause a variety of diseases in different organ systems. Mutations have been described as causing neonatal cholestasis, maturity-onset diabetes of the young (type 5), cortical renal cysts, urogenital abnormalities, liver dysfunction, and atrophy of the pancreas. We describe a male patient who presented with cholestatic liver disease in infancy which progressed by age 14 to end-stage liver disease due to HNF1B disease. He subsequently underwent liver transplantation at age 15 and then developed diabetes requiring insulin which did not resolve after cessation of corticosteroids. To our knowledge, this is the first case reported of liver transplantation for decompensated cirrhosis secondary to HNF1B disease.

Expression, Epigenetic, and Genetic Changes of HNF1B in Colorectal Lesions: an Analysis of 145 Cases.

Hepatocyte nuclear factor 1 beta (HNF1B) is transcription factor which plays a crucial role in the regulation of the development of several organs, but also seems to be implicated in the development of certain tumours, especially the subset of clear cell carcinomas of the ovary and kidney. Depending on the type of the tumour, HNF1B may act as either a tumour suppressor or an oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using immunohistochemical approach and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B on 40 cases of colorectal adenomas and 105 cases of colorectal carcinomas. The expression of HNF1B was correlated with the benign or malignant behaviour of the lesion, given that carcinomas showed significantly lower levels of expression compared to adenomas. In carcinomas, lower levels of HNF1B expression were associated with recurrence and shortened disease-free survival. The mutation analysis revealed three somatic mutations (two frameshift and one nonsense) in the carcinoma sample set. Promoter methylation was detected in three carcinomas. These results suggest that in colorectal cancer, HNF1B may play a part in the pathogenesis and act in a tumour suppressive fashion.

Expression, Epigenetic and Genetic Changes of HNF1B in Endometrial Lesions.

Hepatocyte nuclear factor 1-beta (HNF-1-beta) is a transcription factor involved in cancerogenesis of various tumors, including endometrioid carcinoma. We performed comprehensive analysis of HNF-1-beta in lesions of the endometrium, including protein expression and genetic and epigenetic changes. Expression of HNF-1-beta was analyzed immunohistochemically in 320 cases including both tumor and non-tumor endometrial lesions. Promoter methylation and genetic variants were evaluated, using bisulphite and direct sequencing, in 30 (18 fresh frozen, 12 FFPE tumors) endometrioid carcinomas (ECs) and 15 ovarian clear cell carcinomas (OCCCs) as a control group. We detected expression of HNF-1-beta in 28 % of ECs (51/180 cases), 26 % of serous carcinoma (7/27 cases), 83 % of endometrial clear cell carcinoma (15/18 cases), 93 % of hyperplastic polyps with atypias (13/14 cases), 100 % of hyperplastic polyps without atypias (16/16 cases), 88 % of hyperplasias with atypias (14/16 cases), 91 % of hyperplasias without atypias (10/11 cases), and in ≥80 % of different normal endometrium samples. The control group of OCCCs showed HNF-1-beta expression in 95 % (18/19 cases). Methylation in promoter region was detected in 13.3 % (4/30) of ECs, but not in corresponding normal tissue where available, nor in OCCCs (0/15 cases). Mutation analysis revealed truncating variant c.454C > T (p.Gln152X) in one EC and missense variant c.848C > T (p.Ala283Val) was detected in one OCCC. In conclusion, expression of HNF-1-beta was detected in various extents in all types of lesions analyzed, nevertheless its strong expression was mostly limited to clear cell carcinomas. Biological significance of genetic and epigenetic changes needs further investigation.