2011
DOI: 10.1530/eje-11-0208
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Diabetes caused by insulin gene (INS) deletion: clinical characteristics of homozygous and heterozygous individuals

Abstract: Background: Mutations of the preproinsulin gene (INS) account for both permanent neonatal diabetes (PND) and adult-onset diabetes. The molecular mechanism of complete INS deletion has recently been published and we now add clinical data of homozygous and heterozygous subjects as well as the detailed mapping of the 646 bp deletion of the INS gene.

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Cited by 36 publications
(27 citation statements)
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“…Haploinsufficiency of insulin has been suggested to contribute to the risk for diabetes in heterozygous individuals 19. Thus, our discovery extends the current understanding of how diabetes occurring in neonates may have broader implications for those with insulin deficiency leading to diabetes later in life.…”
Section: Resultsmentioning
confidence: 54%
See 1 more Smart Citation
“…Haploinsufficiency of insulin has been suggested to contribute to the risk for diabetes in heterozygous individuals 19. Thus, our discovery extends the current understanding of how diabetes occurring in neonates may have broader implications for those with insulin deficiency leading to diabetes later in life.…”
Section: Resultsmentioning
confidence: 54%
“…Most other insulin gene mutations, including the only other known intronic mutation (heterozygous c.188-31G>A), lead to misfolded proteins that increase ER stress and β cell death 5 15. Deletions and recessive mutations that lead to reduced insulin biosynthesis have also been described as rare causes of neonatal diabetes 18 19. We describe the first deep intronic homozygous mutation leading to altered splicing and creation of two unstable mutant transcripts.…”
Section: Discussionmentioning
confidence: 96%
“…Recessive INS gene mutations are “loss-of-function” mutations, which affect insulin biosynthesis at transcriptional and/or translational levels through different mechanisms including insulin gene deletion or truncation with failure of insulin transcription; instability of insulin mRNA; or defective translational initiation due to loss of the natural start codon (Garin et al, 2010; Raile et al, 2011). Such mutations may result in a >80% decrease of insulin production from the mutant allele.…”
Section: Diabetogenic Ins-gene Mutations: Recessive Vs Dominant Amentioning
confidence: 99%
“…Before sequencing GATA6 , up-to-date candidate genes known to cause monogenic diabetes and pancreas developmental abnormalities were sequenced ( GCK, HNF1A, HNF1B , HNF4A , INS, ABCC8, KCNJ11, PDX1, PTF1A, ONECUT2, FGF10, SOX17, HLXB9 and HNF6 ). The genotyping methodology was conventional [20]. The 7 exons and neighboring intronic regions of human GATA6 were sequenced in both directions using 11 primer pairs (online suppl.…”
Section: Methodsmentioning
confidence: 99%