ESPE Abstracts (2019) 92 P1-429

Genetic Evaluation of Congenital Hypothyroidism with Gland-In-Situ Using Targeted Exome Sequencing

Jung Hyun Shin1,2, Hye Young Kim1, Young Mi Kim1, Heirim Lee1, Mi Hye Bae1, Kyung Hee Park1, Sae-Mi Lee3, Min Jung Kwak4,2


1Department of Pediatrics, Pusan National University Hospital, Busan, Korea, Republic of. 2Biomedical Research Institute, Pusan National University Hospital, Busan, Korea, Republic of. 3Green Cross Genome, Yongin-si, Korea, Republic of. 4Pusan National University Hospital, Busan, Korea, Republic of


Objective: To analyze the genetic cause of congenital hypothyroidism by targeted exome sequencing in pediatric patients with congenital hypothyroidism with thyroid gland in situ.

Patient and Method: The study population comprised 20 patients with thyroid gland, who were diagnosed with congenital hypothyroidism at Pediatric Endocrinologic Clinic of Pusan National University Hospital. Targeted exome sequencing was performed on 8 causative genes, including the TSHR gene that may be present in the normal thyroid gland and TG, TPO, DUOX2, DUOXA2, IYD, SLC26A4, and SLC5A5 genes that are known to cause thyroid dyshormonogenesis.

Results: Of 20 patients, permanent hypothyroidism, subclinical hypothyroidism, and transient hypothyroidism was found in 15 (75%), 3 (15%), and 2 (10%) patients, respectively. Targeted exome sequencing on 8 genes identified 24 variants among 16 patients: DUOX2 – 11 variants in 8 patients; TSHR – 6 variants in 5 patients; TG – 5 variants in 3 patients; and DUOXA2 – 2 variants in 2 patients. Among these 24 variants, 10 were novel variants. No variants were identified in TPO, IYD, SLC5A5, and SLC26A4 genes. Two patients showed trialleic (digenic) mutations (TG and TSHR in one patient and DUOX2 and TSHR in the other). No variants were identified in 3 patients with permanent hypothyroidism and 1 patient with transient hypothyroidism. Considering inheritance, genetic causes that could explain the phenotypes of congenital hypothyroidism were identified in 11 cases (55%).

Conclusion: Based on the findings, the genetic causes of congenital hypothyroidism by targeted exome sequencing in patients with thyroid gland in situ were identified in 55% of the cases, with DUOX2 and TSHR gene mutation being the most common causes. As there were many novel variants, and the frequency of cases where the genetic mutations were unidentified was high (45%), additional studies on genetic causes of congenital hypothyroidism is warranted.

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