Variable phenotype in HNF1B mutations: extrarenal manifestations distinguish affected individuals from the population with congenital anomalies of the kidney and urinary tract
Por:
Madariaga, L, Garcia-Castano, A, Ariceta, G, Martinez-Salazar, R, Aguayo, A, Castano, L, Garcia-Cuartero, B, Goni, M, Aguirre, M, Gaztambide, S, Gondra, L, Herrero, M, Rica, I, de Nanclares, G, Urrutia, I, de la Piscina, I, Lamas, C, Ubetagoyena, M, Torres, C, Arteaga, R, Gorgojo, J, Badia, J, Chueca, M and Study HNF1B Mutations
Publicada:
1 jun 2019
Resumen:
Background. 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.
Methods. 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.
Results. 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.
Conclusions. 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.
Filiaciones:
Madariaga, L:
Univ Basque Country, Cruces Univ Hosp, Pediat Nephrol Dept, Baracaldo, Spain
Biocruces Hlth Res Inst, Baracaldo, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Garcia-Castano, A:
Biocruces Hlth Res Inst, Baracaldo, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Ariceta, G:
Autonomous Univ Barcelona UAB, Vall Hebron Univ Hosp, Pediat Nephrol Dept, Barcelona, Spain
Martinez-Salazar, R:
Biocruces Hlth Res Inst, Baracaldo, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Aguayo, A:
Biocruces Hlth Res Inst, Baracaldo, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Castano, L:
Univ Basque Country, Cruces Univ Hosp, Pediat Nephrol Dept, Baracaldo, Spain
Biocruces Hlth Res Inst, Baracaldo, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Garcia-Cuartero, B:
Univ Hosp Ramon y Cajal, Madrid, Spain
Goni, M:
Navarra Univ Hosp, Pamplona, Spain
Aguirre, M:
Cruces Univ Hosp, Baracaldo, Spain
Gaztambide, S:
Cruces Univ Hosp, Baracaldo, Spain
Gondra, L:
Cruces Univ Hosp, Baracaldo, Spain
Herrero, M:
Cruces Univ Hosp, Baracaldo, Spain
Rica, I:
Cruces Univ Hosp, Baracaldo, Spain
de Nanclares, G:
Biocruces Hlth Res Inst, Baracaldo, Spain
Urrutia, I:
Biocruces Hlth Res Inst, Baracaldo, Spain
de la Piscina, I:
Biocruces Hlth Res Inst, Baracaldo, Spain
Lamas, C:
Albacete Univ Hosp, Albacete, Spain
Ubetagoyena, M:
Donostia Univ Hosp, San Sebastian, Spain
:
Gen Univ Hosp Elda, Alicante, Spain
Arteaga, R:
Galdakao Hosp, Galdakao, Spain
Gorgojo, J:
Fdn Alcorcon Univ Hosp, Alcorcon, Spain
:
Gen Univ Hosp Castellon, Castellon de La Plana, Spain
Chueca, M:
Virgen Camino Hosp, Pamplona, Spain
Open Access
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