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  Expanded clinical spectrum in hepatocyte nuclear factor 1B-maturity-onset diabetes of the young

Raile, K., Klopocki, E., Holder, M., Wessel, T., Galler, A., Deiss, D., et al. (2009). Expanded clinical spectrum in hepatocyte nuclear factor 1B-maturity-onset diabetes of the young. Journal of Clinical Endocrinology & Metabolism, 94(7), 2658-2664. doi:10.1210/jc.2008-2189.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7D62-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7D63-8
Genre: Journal Article
Alternative Title : J Clin Endocrinol Metab

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 Creators:
Raile, Klemens, Author
Klopocki, Eva1, Author              
Holder, Martin, Author
Wessel, Theda, Author
Galler, Angela, Author
Deiss, Dorothee, Author
Müller, Dominik, Author
Riebel, Thomas, Author
Horn, Denise, Author
Maringa, Monika, Author
Weber, Jürgen, Author
Ullmann, Reinhard2, Author              
Grüters, Annette, Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Molecular Cytogenetics (Reinhard Ullmann), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479645              

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 Abstract: Aims: HNF1B-maturity-onset diabetes of the young is caused by abnormalities in the HNF1B gene encoding the transcription factor HNF-1β. We aimed to investigate detailed clinical features and the type of HNF1B gene anomaly in five pediatric cases with HNF1B-MODY. Methods: From a cohort of 995 children and adolescents with diabetes, we analyzed the most frequent maturity-onset diabetes of the young genes (GCK, HNF1A, HNF4A) including HNF1B sequencing and deletion analysis by quantitative Multiplex-PCR of Short Fluorescent Fragments (QMPSF) if patients were islet autoantibody-negative and had one parent with diabetes or associated extrapancreatic features or detectable C-peptide outside honeymoon phase. Presence and size of disease-causing chromosomal rearrangements detected by QMPSF were further analyzed by array comparative genomic hybridization. Results: Overall, five patients had a heterozygous HNF1B deletion, presenting renal disease, elevated liver enzymes, and diabetes. Diabetes was characterized by insulin resistance and adolescent onset of hyperglycemia. Additionally, clinical features in some patients were pancreas dysplasia and exocrine insufficiency (two of five patients), genital defects (three of five), mental retardation (two of five), and eye abnormalities (coloboma, cataract in two of five). One case also had severe growth deficit combined with congenital cholestasis, and another case had common variable immune deficiency. All patients reported here had monoallelic loss of the entire HNF1B gene. Whole genome array comparative genomic hybridization confirmed a precurrent genomic deletion of approximately 1.3–1.7 Mb in size. Conclusion: The clinical data of our cases enlarge the wide spectrum of patients with HNF1B anomaly. The underlying molecular defect in all cases was a 1.3- to 1.7-Mb deletion, and paired, segmental duplications along with breakpoints were most likely involved in this recurrent chromosomal microdeletion.

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Language(s): eng - English
 Dates: 2009-07
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
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Title: Journal of Clinical Endocrinology & Metabolism
  Alternative Title : J Clin Endocrinol Metab
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 94 (7) Sequence Number: - Start / End Page: 2658 - 2664 Identifier: ISSN: 0021-972X