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Atypical phenotypic features among carriers of a novel Q248X nonsense mutation in the HNF1B gene
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Abstract
Introduction: Hepatocyte transforming factor 1B-maturity onset diabetes mellitus of the young (HNF1B-MODY) is an autosomal dominant type of monogenic diabetes caused by a mutation in the gene encoding hepatocyte nuclear factor 1beta (HNF-1beta). The aim of this study was to determine if a HNF1B gene mutation was responsible for a dominantly inherited form of diabetes mellitus among the members of a three-generation Polish family.
Material and methods: The index subject was a 13-year-old boy with metabolic syndrome, spina bifida occulta, posterior urethral valves, congenital ureteropelvic junction obstruction, and a family history of diabetes of autosomal dominant trait of inheritance. We performed clinical and laboratory examinations of his family and sequenced the HNF1B gene.
Results: A novel Q248X mutation (nucleotide C to T transition at position 742 of the exon 3 of HNF1B gene, resulting in stop codon formation) was identified. Phenotypes of family members sharing this mutation are highly variable, and include previously known abnormalities of the urinary system and pancreas, diabetes mellitus of variable onset and severity, hyperinsulinaemia, insulin resistance, metabolic syndrome, elevated aminotransferases, hyperbilirubinemia, hyperamylasemia, short stature and cataracts. To the best of our knowledge, spina bifida occulta, pectus carinatum, and splenomegaly have not been previously reported.
Conclusions: Our results broaden the spectrum of HNF1B gene mutations and HNF1B-MODY-related phenotypes.
Abstract
Introduction: Hepatocyte transforming factor 1B-maturity onset diabetes mellitus of the young (HNF1B-MODY) is an autosomal dominant type of monogenic diabetes caused by a mutation in the gene encoding hepatocyte nuclear factor 1beta (HNF-1beta). The aim of this study was to determine if a HNF1B gene mutation was responsible for a dominantly inherited form of diabetes mellitus among the members of a three-generation Polish family.
Material and methods: The index subject was a 13-year-old boy with metabolic syndrome, spina bifida occulta, posterior urethral valves, congenital ureteropelvic junction obstruction, and a family history of diabetes of autosomal dominant trait of inheritance. We performed clinical and laboratory examinations of his family and sequenced the HNF1B gene.
Results: A novel Q248X mutation (nucleotide C to T transition at position 742 of the exon 3 of HNF1B gene, resulting in stop codon formation) was identified. Phenotypes of family members sharing this mutation are highly variable, and include previously known abnormalities of the urinary system and pancreas, diabetes mellitus of variable onset and severity, hyperinsulinaemia, insulin resistance, metabolic syndrome, elevated aminotransferases, hyperbilirubinemia, hyperamylasemia, short stature and cataracts. To the best of our knowledge, spina bifida occulta, pectus carinatum, and splenomegaly have not been previously reported.
Conclusions: Our results broaden the spectrum of HNF1B gene mutations and HNF1B-MODY-related phenotypes.
Keywords
hepatocyte nuclear factor 1-beta; HNF1B-MODY; pectus carinatum; phenotype; spina bifida occulta; splenomegaly; Q248X mutation
About this articleTitle
Atypical phenotypic features among carriers of a novel Q248X nonsense mutation in the HNF1B gene
Journal
Issue
Article type
Original paper
Pages
15-21
Published online
2015-03-02
Page views
1948
Article views/downloads
2370
DOI
10.5603/EP.2015.0004
Pubmed
Bibliographic record
Endokrynol Pol 2015;66(1):15-21.
Keywords
hepatocyte nuclear factor 1-beta
HNF1B-MODY
pectus carinatum
phenotype
spina bifida occulta
splenomegaly
Q248X mutation
Authors
Anna Hogendorf
Małgorzata Kosińska-Urbańska
Maciej Borowiec
Karolina Antosik
Krystyna Wyka
Wojciech Młynarski
