Abstract
Disclosure: J. Ahn: None. H. Jeong: None. Background: Guidelines on congenital hypothyroidism (CH) recommend that genetic testing should aim to improve diagnosis, treatment or prognosis. Little information is available regarding the genetic heterogeneity of CH in Koreans. We aimed to investigate the genetic etiology of permanent CH to increase the genetic diagnosis rate and find associated diseases by whole exome sequencing (WES). Methods: A total of 32 patients with permanent CH were enrolled from Endocrinology Clinic at Jeju National University Hospital and Soonchunhyang University Cheonan Hospital. WES was performed on 3billion extracted through the patient's buccal swab. Variant classification is based on the guidelines presented by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP). Results: A total of 30 variants were identified in 20 patients. (62%). WES identified 22 variants in 6 genes (DUOX2, DUOXA2, TPO, PAX8, TG, TSHR). We detected 20 Pathogenic /Likely pathogenic of 5 genes in 15 patients (50%). The most frequently affected genes were DUOX2 (n = 10), TPO(n=4) DUOXA2 (n=3), TSHR(n=3)and PAX8 (n=2). 16 patients are monogenic and 4 patients have oligo-genic mutations. The test results of patients (n=6) with thyroid agenesis or ectopic thyroid gland were all negative. Conclusions: In patients with permanent congenital hypothyroidism, the mutation rate through the WES method is quite high. Genetic testing is useful for medication dose adjustment and genetic counseling through correlation of genotype and phenotype. Presentation: 6/1/2024