ArticleDiabetes2009
Severe insulin resistance and intrauterine growth deficiency associated with haploinsufficiency for INSR and CHN2: new insights into synergistic pathways involved in growth and metabolism.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Trial
- A KDM6 A variant in a Chinese female patient with diabetes mellitus and oligomenorrhea: a case report.Journal of medical case reports · 2025Article
- β2-Chimaerin, a GTPase-Activating Protein for Rac1, Is a Novel Regulator of Hepatic Insulin Signaling and Glucose Metabolism.Molecules (Basel, Switzerland) · 2024Article
- DNA methylation in diabetic retinopathy: pathogenetic role and potential therapeutic targets.Cell & bioscience · 2022Review
- Salivary epigenetic biomarkers as predictors of emerging childhood obesity.BMC medical genetics · 2020Article
- Article
- Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity.BMC genomics · 2017Article
- A new role of the Rac-GAP β2-chimaerin in cell adhesion reveals opposite functions in breast cancer initiation and tumor progression.Oncotarget · 2016Article
- Article
- Successful rhIGF1 treatment for over 5 years in a patient with severe insulin resistance due to homozygous insulin receptor mutation.Diabetic medicine : a journal of the British Diabetic Association · 2016Article
- Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans.PloS one · 2016Article
- Successful pregnancy outcomes in a patient with type A insulin resistance syndrome.Diabetic medicine : a journal of the British Diabetic Association · 2015Article
- Severe insulin resistance alters metabolism in mesenchymal progenitor cells.Endocrinology · 2015Article
- Sequencing analysis of insulin receptor defects and detection of two novel mutations inMolecular genetics and metabolism reports · 2014Article
- Comparison of serum maternal adiponectin concentrations in women with isolated intrauterine growth retardation and intrauterine growth retardation concomitant with pre-eclampsia.Journal of the Turkish German Gynecological Association · 2014Article
- Pleiotropy and pathway analyses of genetic variants associated with both type 2 diabetes and prostate cancer.International journal of molecular epidemiology and genetics · 2013Article
- Coordinated activation of the Rac-GAP β2-chimaerin by an atypical proline-rich domain and diacylglycerol.Nature communications · 2013Article
- Longitudinal genome-wide association of cardiovascular disease risk factors in the Bogalusa heart study.PLoS genetics · 2010Article
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
objectiveDigenic causes of human disease are rarely reported. Insulin via its receptor, which is encoded by INSR, plays a key role in both metabolic and growth signaling pathways. Heterozygous INSR mutations are the most common cause of monogenic insulin resistance. However, growth retardation is only reported with homozygous or compound heterozygous mutations. We describe a novel translocation [t(7,19)(p15.2;p13.2)] cosegregating with insulin resistance and pre- and postnatal growth deficiency. Chromosome translocations present a unique opportunity to identify modifying loci; therefore, our objective was to determine the mutational mechanism resulting in this complex phenotype. RESEARCH DESIGN AND
methodsBreakpoint mapping was performed by fluorescence in situ hybridization (FISH) on patient chromosomes. Sequencing and gene expression studies of disrupted and adjacent genes were performed on patient-derived tissues. RESULTS Affected individuals had increased insulin, C-peptide, insulin-to-C-peptide ratio, and adiponectin levels consistent with an insulin receptoropathy. FISH mapping established that the translocation breakpoints disrupt INSR on chromosome 19p15.2 and CHN2 on chromosome 7p13.2. Sequencing demonstrated INSR haploinsufficiency accounting for elevated insulin levels and dysglycemia. CHN2 encoding beta-2 chimerin was shown to be expressed in insulin-sensitive tissues, and its disruption was shown to result in decreased gene expression in patient-derived adipose tissue.
conclusionsWe present a likely digenic cause of insulin resistance and growth deficiency resulting from the combined heterozygous disruption of INSR and CHN2, implicating CHN2 for the first time as a key element of proximal insulin signaling in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.