Background: A 46-year-old Qatari female with a BMI of 25kg/m2 presented with hyperglycemia (blood glucose 13.5 mmol/l), hyperinsulinemia (21µU/mL) with elevated levels of HbA1c (10.3mmol/l). Biochemical investigations showed raised serum C-peptide (2.02ng/ml) and triglycerides (2.07mmol/L) and uric acid (104mg/dL), with normal BP. The objective of this case study is to validate this variant found through WGS in insulin receptor (INSR) gene that play a major cause of insulin resistant syndrome with different spectrums.

Methods: Structural Variants discovered using custom multi-algorithm pipeline developed and optimized to run on HPC for short-read WGS data. In brief, 10 software packages applied (Breakdancer, Breakseq2, CNVnator, Delly, ERDS, Genomestrip, Manta, Speedseq, Svaba, WHAM), to existing short-read data. SVs annotated using AnnotSV and provides us functionally, regulatory and clinically relevant information. SVs analyzed based on their properties like pli-score, overlaps with known databases and OMIM annotations. This deletion was validated by ddPCR and the molecular docking performed by the autodock suit in order to understand the effect of deletion in the interaction between this receptor and insulin.

Results: The patient was identified with 7.2k heterozygous deletion in exon 8 of INSR gene which play an essential role in the formation of extracellular alpha subunits in insulin receptor. molecular docking proved the decrease of catalytic activity of INSR and, hence signaling. Considering this and the phenotypic data from Qatar biobank, the patient developed features of type A insulin resistant syndrome as consequence of persistence hyperinsulinemia. The patient also exhibits severe Deterioration of glucose tolerant even with medication and unfortunately developed nephropathy.

Conclusion: We highlighted the power of NGS in precise diagnosis and developing a potential and promising targeted therapeutics.


A.S. Akil: None. E.A.M. Yassin: None. S. Subash Padmajeya: None. L.A. Jerman: None. A. Fadda: None. W.H.O. Aamer: None. E.E. Aliyev: None. K. Fakhro: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at