Читать книгу Clinical Obesity in Adults and Children - Группа авторов - Страница 75

Albright hereditary osteodystrophy (AHO) is an autosomal dominant disorder due to inactivating mutations in GNAS1, the gene encoding Gαs, the G protein that couples receptors to adenylyl cyclase leading to cAMP generation. Heterozygous loss‐of‐function mutations lead to AHO, a disease characterized by short stature, obesity, skeletal defects, and developmental delay. Maternal transmission of GNAS1 mutations leads to AHO plus resistance to several hormones (e.g. parathyroid hormone) that activate Gαs in their target tissues, while paternal transmission leads only to the AHO phenotype. Studies in both mice and humans demonstrate that GNAS1 is imprinted in a tissue‐specific manner, being expressed primarily from the maternal allele in some tissues and biallelically in most other tissues; thus, multihormone resistance occurs only when GNAS mutations are inherited maternally [17]. Patients can present with severe obesity alone; the other classical features can emerge over time in some but not all patients.