A novel nonsense mutation in the insulin receptor gene in a patient with HAIR-AN syndrome and endometrial cancer

• Published in: Molecular genetics and metabolism reports Vol. 35; p. 100965
• Main Authors: Cuenca, Dalia, Ventura-Gallegos, Jose Luis, Almeda-Valdes, Paloma, Tusié-Luna, María Teresa, Reza-Albarran, Alfredo, Ventura-Ayala, Laura, Ordoñez-Sánchez, Ma. Luisa, Segura-Kato, Yayoi, Gomez-Perez, Francisco Javier, Conte, Michelle De Puy, Gonzalez, Lizbet Ruilova, Zentella-Dehesa, Alejandro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2023; Elsevier
• Subjects: Case Report; PCOS; OGTT; PBMC; INSR; PCOS, Polycystic ovary syndrome; OGTT, Oral glucose tolerance test; PBMC, Peripheral blood mononuclear cells; INSR, Insulin receptor
• ISSN: 2214-4269; 2214-4269
• DOI: 10.1016/j.ymgmr.2023.100965

Severe insulin resistance can be caused by rare genetic defects in the insulin receptor known as insulin receptoropathies. These genetic defects cause a wide spectrum of clinical manifestations ranging from mild syndromes to lethal disorders. Among those is the HAIR-AN an extreme subtype of polycystic ovary syndrome (PCOS). We present a case of a 29-year-old woman with amenorrhea, severe insulin resistance, hirsutism, and acanthosis nigricans who also developed endometrial cancer. She was found to carry a novel heterozygous nonsense mutation insulin receptor gene (INSR). The mutation was inherited from the mother. Levels of insulin receptor and AKT were measured using Western-Blot from peripheral blood mononuclear cells and were both decreased. Thus, we conclude that the identified mutation in the insulin receptor gene and lead to decreased activity of the downstream signaling of the insulin pathway. •Mutations in the insulin receptor gene can cause syndromes of severe insulin resistance known as insulin receptoropathies.•HAIR-AN syndrome is a severe subtype of polycystic ovarian syndrome.•High levels of adiponectin in the context of insulin resistance, are suggestive for insulin receptoropathies.