Background/Aims: This study aimed to identify, clinically and molecularly, the causality of Rabson-Mendenhall syndrome in an Emirati family. It is one of the monogenic syndromes of abnormal glucose homeostasis, which result from insulin receptor defects. Methods: A novel nonsynonymous variant in the INSR gene was uncovered by whole exome sequencing and confirmed using Sanger sequencing in the patient and his parents. Various in silico tools were utilized to analyze the functional consequences of the variant. Results: Results revealed a previously unreported INSR variant in the family: c.421C>T (p.Arg141Trp). Homozygosity for the variant was found in the patient, while both parents were heterozygous. Conclusion: The nonsynonymous protein change hit a highly conserved arginine residue in the insulin-binding α-subunit of the receptor and was deemed ‘functionally damaging' by a myriad of bioinformatics tools. This report is a step forward along the way of achieving a better molecular and clinical characterization of Rabson-Mendenhall syndrome.

Keywords:
Genetic syndromes, Mutation, Insulin resistance, Monogenic diabetes, Insulin signaling
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© 2016 S. Karger AG, Basel
2016
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