Partial and whole gene deletion mutations of the GCK and HNF1A genes in maturity-onset diabetes of the young

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dc.contributor.authorEllard S.
dc.contributor.authorThomas K.
dc.contributor.authorEdghill E.L.
dc.contributor.authorOwens M.
dc.contributor.authorAmbye L.
dc.contributor.authorCropper J.
dc.contributor.authorLittle J.
dc.contributor.authorStrachan M.
dc.contributor.authorStride A.
dc.contributor.authorErsoy B.
dc.contributor.authorEiberg H.
dc.contributor.authorPedersen O.
dc.contributor.authorShepherd M.H.
dc.contributor.authorHansen T.
dc.contributor.authorHarries L.W.
dc.contributor.authorHattersley A.T.
dc.date.accessioned2024-07-22T08:22:44Z
dc.date.available2024-07-22T08:22:44Z
dc.date.issued2007
dc.description.abstractAims/hypothesis: Heterozygous mutations of glucokinase (GCK) and hepatocyte nuclear factor-1 alpha (HNF1A; also known as hepatic transcription factor 1 [TCF1]) genes are the most common cause of MODY. Genomic deletions of the HNF1B (also known as TCF2) gene have recently been shown to account for one third of mutations causing renal cysts and diabetes syndrome. We investigated the prevalence of partial and whole gene deletions in UK patients meeting clinical criteria for GCK or HNF-1α/-4α MODY and in whom no mutation had been identified by sequence analysis. Methods: A multiplex ligation-dependent probe amplification (MLPA) assay was developed using synthetic oligonucleotide probes for 30 exons of the GCK, HNF1A and HNF4A genes. Partial or whole gene deletions were identified in 1/29 (3.5%) probands using the GCK MLPA assay and 4/60 (6.7%) of probands using the HNF1A/-4A MLPA assay. Four different deletions were detected: GCK exon 2, HNF1A exon 1, HNF1A exons 2 to 10 and HNF1A exons 1 to 10. An additional Danish pedigree with evidence of linkage to HNF1A had a deletion of exons 2 to 10. Testing other family members confirmed co-segregation of the deletion mutations with diabetes in the pedigrees. Conclusions/interpretation: Large deletions encompassing whole exons can cause GCK or HNF-1α MODY and will not be detected by sequencing. Gene dosage assays, such as MLPA, are a useful adjunct to sequence analysis when a diagnosis of MODY is strongly suspected. © 2007 Springer-Verlag.
dc.identifier.DOI-ID10.1007/s00125-007-0798-6
dc.identifier.issn0012186X
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/19212
dc.language.isoEnglish
dc.rightsAll Open Access; Bronze Open Access
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAge of Onset
dc.subjectChild, Preschool
dc.subjectDiabetes Mellitus, Type 2
dc.subjectFemale
dc.subjectGene Deletion
dc.subjectGlucokinase
dc.subjectHepatocyte Nuclear Factor 1-alpha
dc.subjectHumans
dc.subjectMale
dc.subjectPedigree
dc.subjectPhenotype
dc.subjectglucokinase
dc.subjecthepatocyte nuclear factor 1alpha
dc.subjecttranscription factor 7
dc.subjectadolescent
dc.subjectadult
dc.subjectarticle
dc.subjectchild
dc.subjectexon
dc.subjectfamily relation
dc.subjectgene amplification
dc.subjectgene deletion
dc.subjectgene mutation
dc.subjectgenetic analysis
dc.subjecthuman
dc.subjectjuvenile diabetes mellitus
dc.subjectoligonucleotide probe
dc.subjectpedigree analysis
dc.subjectpriority journal
dc.subjectsequence analysis
dc.titlePartial and whole gene deletion mutations of the GCK and HNF1A genes in maturity-onset diabetes of the young
dc.typeArticle

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