Identification of a Novel Mutation in Patients with Type A Insulin Resistance Syndrome

Introduction: Type A insulin resistance syndrome is a rare type of congenital insulin resistance often caused by heterozygous mutations in the insulin receptor gene (INSR). The aim of this study was to explore the clinical and genetic characteristics of three patients with type A insulin resistance syndrome from two Chinese families. Methods: The peripheral blood samples were collected from each family member. Whole-exome sequencing was performed on three patients. Results: Patient #1 was diagnosed with hyperinsulinemia at the age of 11 years and presented with hirsutism, acanthosis nigricans, and polycystic ovaries by 13 years. A heterozygous c.3470A>G mutation in the INSR gene was identified in patient #1. Patient #2 was a 13-year-old girl who presented with insulin resistance, polycystic ovary, and hyperandrogenemia. A novel c.3601C>G INSR mutation was identified in patient #2. Co-segregated analysis showed that the c.3601C>G mutation was also found in her father, who had hyperinsulinemia and diabetes mellitus, which was consistent with autosomal dominant inheritance. SIFT and PolyPhen-2 predicted that the c.3470A>G and c.3601C>G mutations in INSR had damaging effects. Conclusion: Our study expands the genotypic and phenotypic spectrum of type A insulin resistance syndrome. Awareness of the clinical features coupled with INSR gene screening is key to early detection and active intervention.