A follow-up during puberty in a Japanese girl with type A insulin resistance due to a novel mutation in INSR

The human insulin receptor is encoded by a single gene with 22 exons, and it is a membrane protein composed of two α and two β subunits (1). Binding of insulin to the extracellular α subunit causes a conformational change, leading to the activation of tyrosine kinase at the intracellular β subunit as well as the autophosphorylation of the receptor, followed by the activation of signal transduction cascades. Mutations in the gene encoding the insulin receptor (INSR) result in the insulin-resistant syndromes such as Leprechaunism, also known as the Donohue syndrome, as well as the Rabson-Mendenhall syndrome and type A insulin resistance (IR) (2). The former two syndromes are autosomal recessive disorders and characterized by severe phenotypes including intrauterine and postnatal growth retardation, dysmorphic features, altered glucose homeostasis, and early mortality. On the other hand, type A IR is an autosomal dominant disorder and is characterized by IR, acanthosis nigricans (AN), and hyperandrogenism such as polycystic ovarian syndrome (PCOS). To date, more than 100 disease-causing mutations have already been reported (2). Among them, approximately half of the mutations were identified in type A IR. Type B IR is an autoimmune disorder characterized by the presence of the insulin receptor antibody. Here, we described a clinical course from childhood to puberty in a Japanese girl with type A IR due to a novel nonsense mutation in INSR.