Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance

Summary We report a case of an 11-year-old girl presenting with a new diagnosis of diabetes associated with a heterozygous missense mutation in the insulin receptor (INSR) gene. This case highlights that INSR gene variants can be a cause for monogenic diabetes in children and adolescents and the need for genetic evaluation in atypical presentations of diabetes. We also describe the possible role of metformin in treating individuals with type A insulin resistance syndrome due to INSR gene variants. Learning points Insulin receptor (INSR) gene variants can be a cause of monogenic diabetes in children and adolescents. Genetic evaluation should be considered in children and adolescents with type 2 diabetes (T2D), particularly where there is an atypical presentation and/or positive family history. Metformin may have a role in the treatment of type A insulin resistance syndrome due to heterozygous mutation of the INSR gene.

Estimation of Pool Construction and Technical Error

Pooling animals with extreme phenotypes can improve the accuracy of genetic evaluation or provide genetic evaluation for novel traits at relatively low cost by exploiting large amounts of low-cost phenotypic data from animals in the commercial sector without pedigree (data from commercial ranches, feedlots, stocker grazing or processing plants). The average contribution of each animal to a pool is inversely proportional to the number of animals in the pool or pool size. We constructed pools with variable planned contributions from each animal to approximate errors with different numbers of animals per pool. We estimate pool construction error based on combining liver tissue, from pulverized frozen tissue mass from multiple animals, into eight sub-pools containing four animals with planned proportionality (1:2:3:4) by mass. Sub-pools were then extracted for DNA and genotyped using a commercial array. The extracted DNA from the sub-pools was used to form super pools based on DNA concentration as measured by spectrophotometry with planned contribution of sub-pools of 1:2:3:4. We estimate technical error by comparing estimated animal contribution using sub-samples of single nucleotide polymorphism (SNP). Overall, pool construction error increased with planned contribution of individual animals. Technical error in estimating animal contributions decreased with the number of SNP used.