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- Title
Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations.
- Authors
Bellanné-Chantelot C; Chauveau D; Gautier J; Dubois-Laforgue D; Clauin S; Beaufils S; Wilhelm J; Boitard C; Noël L; Velho G; Timsit J; Bellanné-Chantelot, Christine; Chauveau, Dominique; Gautier, Jean-François; Dubois-Laforgue, Danièle; Clauin, Séverine; Beaufils, Sandrine; Wilhelm, Jean-Marie; Boitard, Christian; Noël, Laure-Hélène
- Abstract
<bold>Background: </bold>Maturity-onset diabetes of the young type 5 (MODY5), a type of dominantly inherited diabetes mellitus and nephropathy, has been associated with mutations of the hepatocyte nuclear factor-1beta (HNF-1beta) gene, mostly generating truncated protein. Various phenotypes, including urogenital malformations, are related to HNF-1beta mutations.<bold>Objective: </bold>To describe clinical and genetic findings in 13 patients with 8 novel HNF-1beta mutations.<bold>Design: </bold>Multicenter, descriptive study.<bold>Setting: </bold>2 departments of diabetes, 1 department of internal medicine, and 1 department of nephrology.<bold>Participants: </bold>8 probands with diabetes diagnosed before 40 years of age and nondiabetic kidney disease who were selected independent of their family history of diabetes, and 5 offspring.<bold>Measurements: </bold>Characteristics of diabetes, renal function and structure, genital tract abnormalities, pancreas structure, insulin secretion, exocrine pancreas function, and liver test results.<bold>Results: </bold>All mutations, including 5 missense changes, were found in the DNA-binding domain. Cosegregation of the mutation and MODY5 phenotype was observed in 4 families. Occurrence of a de novo mutation was demonstrated in 2 families. Diabetes was present in 10 of 13 mutation carriers. It was clinically overt in 5 participants and found by screening at age 19 to 38 years in 5 participants. Pancreas atrophy was observed in 5 of 6 probands, and pancreas exocrine insufficiency was observed in 6 of 7 probands. Renal involvement, consisting of structural changes and slowly progressive renal failure, was recognized in 9 patients at 18 to 41 years of age. Dysplastic kidneys were found by ultrasonography in 3 fetuses who subsequently showed transient neonatal renal failure. Genital tract abnormalities were present in 5 probands and liver enzyme levels were abnormal in 11 of 13 patients.<bold>Limitations: </bold>Since the study was small and not population-based, it could not estimate the prevalence of MODY5. Other phenotypes might be associated with HNF-1beta mutations.<bold>Conclusions: </bold>Maturity-onset diabetes of the young type 5 encompasses a wide clinical spectrum. Analysis for mutations of HNF-1beta is warranted, even without a family history of diabetes, in nonobese patients with diabetes and slowly progressive nondiabetic nephropathy, particularly when pancreatic atrophy or genital abnormalities are present.
- Publication
Annals of Internal Medicine, 2004, Vol 140, Issue 7, p510
- ISSN
0003-4819
- Publication type
journal article
- DOI
10.7326/0003-4819-140-7-200404060-00009