Maturity-onset diabetes of the young caused by a balanced translocation where the 20q12 break point results in disruption upstream of the coding region of hepatocyte nuclear factor-4alpha (HNF4A) gene.

2.50
Hdl Handle:
http://hdl.handle.net/11287/619730
Title:
Maturity-onset diabetes of the young caused by a balanced translocation where the 20q12 break point results in disruption upstream of the coding region of hepatocyte nuclear factor-4alpha (HNF4A) gene.
Authors:
Gloyn, A. L.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Shepherd, Maggie ( 0000-0003-2660-0955 ) ; Howell, R. T.; Parry, E. M.; Jefferson, A.; Levy, E. R.; Hattersley, Andrew T.
Abstract:
Monogenic human disorders have been used as paradigms for complex genetic disease and as tools for establishing important insights into mechanisms of gene regulation and transcriptional control. Maturity-onset diabetes of the young (MODY) is a monogenic dominantly inherited form of diabetes that is characterized by defective insulin secretion from the pancreatic beta-cells. A wide variety of mutation types in five different genes have been identified that result in this condition. There have been no reports of a chromosome deletion or translocation resulting in MODY. We report a pedigree where MODY cosegregates with a balanced translocation [karyotype 46, XX t(3;20) (p21.2;q12)]. The chromosome 20 break point, 20q12, is within the region of one of the known MODY genes, hepatocyte nuclear factor-4alpha (HNF4A). Fluorescence in situ hybridization analysis demonstrated that the break point does not disrupt the coding region of this gene, but it lies at least 6 kb upstream of the conventional promoter (P1). We propose that this mutation disrupts the spatial relationship between the recently described alternate distal pancreatic promoter (P2) and HNF4A. This is the first case of MODY due to a balanced translocation, and it provides evidence to confirm the crucial role of an upstream regulator of HNF4A gene expression in the beta-cell.
Citation:
Maturity-onset diabetes of the young caused by a balanced translocation where the 20q12 break point results in disruption upstream of the coding region of hepatocyte nuclear factor-4alpha (HNF4A) gene. 2002, 51 (7):2329-33 Diabetes
Publisher:
Highwire
Journal:
Diabetes
Issue Date:
Jul-2002
URI:
http://hdl.handle.net/11287/619730
PubMed ID:
12086970
Additional Links:
http://diabetes.diabetesjournals.org/content/51/7/2329.long
Note:
This article is freely available via Open Access. Click on the ‘Additional Link’ above to access the full-text from the publisher’s site.
Type:
Case Report; Research Support, Non-U.S. Gov't
Language:
en
ISSN:
0012-1797
Appears in Collections:
pre-2014 RD&E publications; Diabetes/Endocrine Services; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorGloyn, A. L.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorShepherd, Maggieen
dc.contributor.authorHowell, R. T.en
dc.contributor.authorParry, E. M.en
dc.contributor.authorJefferson, A.en
dc.contributor.authorLevy, E. R.en
dc.contributor.authorHattersley, Andrew T.en
dc.date.accessioned2016-09-02T11:19:51Z-
dc.date.available2016-09-02T11:19:51Z-
dc.date.issued2002-07-
dc.identifier.citationMaturity-onset diabetes of the young caused by a balanced translocation where the 20q12 break point results in disruption upstream of the coding region of hepatocyte nuclear factor-4alpha (HNF4A) gene. 2002, 51 (7):2329-33 Diabetesen
dc.identifier.issn0012-1797-
dc.identifier.pmid12086970-
dc.identifier.urihttp://hdl.handle.net/11287/619730-
dc.description.abstractMonogenic human disorders have been used as paradigms for complex genetic disease and as tools for establishing important insights into mechanisms of gene regulation and transcriptional control. Maturity-onset diabetes of the young (MODY) is a monogenic dominantly inherited form of diabetes that is characterized by defective insulin secretion from the pancreatic beta-cells. A wide variety of mutation types in five different genes have been identified that result in this condition. There have been no reports of a chromosome deletion or translocation resulting in MODY. We report a pedigree where MODY cosegregates with a balanced translocation [karyotype 46, XX t(3;20) (p21.2;q12)]. The chromosome 20 break point, 20q12, is within the region of one of the known MODY genes, hepatocyte nuclear factor-4alpha (HNF4A). Fluorescence in situ hybridization analysis demonstrated that the break point does not disrupt the coding region of this gene, but it lies at least 6 kb upstream of the conventional promoter (P1). We propose that this mutation disrupts the spatial relationship between the recently described alternate distal pancreatic promoter (P2) and HNF4A. This is the first case of MODY due to a balanced translocation, and it provides evidence to confirm the crucial role of an upstream regulator of HNF4A gene expression in the beta-cell.en
dc.language.isoenen
dc.publisherHighwireen
dc.relation.urlhttp://diabetes.diabetesjournals.org/content/51/7/2329.longen
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleMaturity-onset diabetes of the young caused by a balanced translocation where the 20q12 break point results in disruption upstream of the coding region of hepatocyte nuclear factor-4alpha (HNF4A) gene.en
dc.typeCase Reporten
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalDiabetesen
dc.description.noteThis article is freely available via Open Access. Click on the ‘Additional Link’ above to access the full-text from the publisher’s site.en
dc.type.versionPublisheden

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