[abstract to accompany Clinical Endocrinology Journal Early-Career Research Award application]
The precision medicine revolution with genotype-based prognostication and management compels us to improve the molecular diagnosis of endocrinopathies in our patients. This may be achieved by finding new causative genes and/or by refined genetic testing to improve variant detection in known genes. Through a number of recently completed and ongoing multicentre interdisciplinary Australian collaborations, we are decoding the genomic architecture of endocrinopathies using contemporary next-generation sequencing and bioinformatic methodologies.
Recent major outcomes include the identification and ongoing characterisation of novel pituitary tumorigenesis genes (e.g., PAM, CHEK2 ) (1, 2), new applications of known gene-disease relationships (e.g., BRAF in craniopharyngiomas, GCK in suspected monogenic diabetes), demonstration of novel variant types in established predisposition genes (e.g., copy number variation, deep intronic variants) (3, 4), and examination of the interplay between ethnicity and inherited endocrinopathies (e.g., white European vs. non-white European ethnicity in monogenic diabetes, hereditary pancreatitis in Indigenous Australians) (4, 5). New gene-disease relationships continue to be explored through whole exome/genome projects in the monogenic diabetes and hereditary pancreatitis settings.
To translate these scientific advances into improved diagnostic pathways, these data are being actively disseminated through the broad endocrinology, genetic pathology and clinical genetics communities via the development of cross-specialty guidelines (6) and national endocrine genetics multidisciplinary meetings run by the EndoGen network. Enhancing the molecular diagnosis of endocrinopathies at the basic scientific and clinical levels will be vital in delivering precision endocrinology to affected individuals and their families.