Variable phenotype in HNF1B mutations : extrarenal manifestations distinguish affected individuals from the population with congenital anomalies of the kidney and urinary tract
Madariaga, Leire (Centro de Investigación Biomédica en Red de Enfermedades Raras)
García-Castaño, Alejandro (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Ariceta Iraola, Gema (Hospital Universitari Vall d'Hebron)
Martínez-Salazar, Rosa (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Aguayo, Aníbal (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Castaño, Luis (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Universitat Autònoma de Barcelona

Fecha:	2018
Resumen:	Mutations in hepatocyte nuclear factor 1B (HNF1B) have been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Diabetes and other less frequent anomalies have also been described. Variable penetrance and intrafamilial variability have been demonstrated including severe prenatal phenotypes. Thus, it is important to differentiate this entity from others with similar clinical features and perform confirmatory molecular diagnosis. This study reports the results of HNF1B screening in a cohort of 60 patients from 58 unrelated families presenting with renal structural anomalies and/or non-immune glucose metabolism alterations, and other minor features suggesting HNF1B mutations. This study identified a pathogenic variant in 23 patients from 21 families. The most frequent finding was bilateral cystic dysplasia or hyperechogenic kidneys (87% of patients). Sixty percent of them also fulfilled the criteria for impaired glucose metabolism, and these were significantly older than those patients with an HNF1B mutation but without diabetes or prediabetes (14. 4 versus 3. 3 years, P < 0. 05). Furthermore, patients with HNF1B mutations had higher frequency of pancreatic structural anomalies and hypomagnesaemia than patients without mutations (P < 0. 001 and P = 0. 003, respectively). Hyperuricaemia and increased liver enzymes were detected in some patients as well. Renal anomalies found in patients with HNF1B mutations are frequently unspecific and may resemble those found in other renal pathologies (CAKUT, ciliopathies). Active searching for extrarenal minor features, especially pancreatic structural anomalies or hypomagnesaemia, could support the indication for molecular diagnosis to identify HNF1B mutations.
Ayudas:	Instituto de Salud Carlos III PI09-90888 Instituto de Salud Carlos III PI11-0141 Instituto de Salud Carlos III PS09-0149
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	CAKUT ; HNF1B ; Hypomagnesaemia ; MODY ; Pancreatic structural anomalies
Publicado en:	Clinical Kidney Journal, Vol. 12 (november 2018) , p. 373-379, ISSN 2048-8513

DOI: 10.1093/ckj/sfy102
PMID: 31198537

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