Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes.

Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Research Abstract Details 

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Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Abstract Text:

The generation of multiple transcripts by mRNA processing has the potential to moderate differences in gene expression both between tissues and at different stages of development. Where gene function is compromised by mutation, the presence of multiple isoforms may influence the resulting phenotype. Heterozygous mutations in the transcription factor hepatocyte nuclear factor-1 alpha (HNF1A or TCF1 gene) result in early-onset diabetes as a result of pancreatic beta-cell dysfunction. We investigated the expression of the three alternatively processed isoforms of the HNF1A gene and their impact on the phenotype associated with mutations. Real-time PCR demonstrated variation in tissue expression of HNF1A isomers: HNF1A(A), with the lowest transactivation activity compared with the truncated isoforms HNF1A(B) and HNF1A(C), is the major isomer in liver (54%) and kidney (67%) but not in adult pancreas (24%) and islets (26%). However, in fetal pancreas HNF1A(A) is the major transcript (84%), which supports developmental regulation of isomer expression. We examined whether the isomers affected by the mutation altered the diabetes phenotype in 564 subjects with 123 mutations in HNF1A. Mutations that affected only isomer HNF1A(A) (exons 8-10) were diagnosed later (25.5 years) than mutations affecting all three isomers (exons 1-6) (18.0 years) (P=0.006). This first genotype/phenotype relationship described for patients with HNF1A mutations is explained by isomer structure and not by either mutation type or functional domain. We conclude that all three isomers may be critical for beta-cell function and could play a role in both the developing and mature beta cell.

Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Publishing Authors By Initials

For similar nucleic acids, nucleotides, and nucleosides: nucleic acids: rna: rna, messenger research abstracts see: nucleic acids, nucleotides, and nucleosides: nucleic acids: rna: rna, messenger research

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Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Human molecular genetics

VOLUME: 15

Page Numbers: 2216-24

Journal Abbreviation: Hum. Mol. Genet.

ISSN: 0964-6906

DAY: 7

MONTH: 06

YEAR: 2006

Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Information

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LANGUAGE: eng

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Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Keywords Mesh Terms:

KEYWORDS: RNA, Messenger

MESH TERMS: metabolism

Chemical & Substance for Abstract: Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Information

Substance Name: RNA, Messenger

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Grant and Affiliation Information for Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes.

AFFILIATION: Institute of Biomedical and Clincal Sciences, Peninsula Medical School, Barrack Road, Exeter, Devon, UK. l.w.harries@exeter.ac.uk

Country: England

AGENCY: United Kingdom Wellcome T

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MEDLINETA: Hum Mol Genet

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