ESPE Abstracts

Introduction: Congenital hypothyroidism (CH) is caused by underdeveloped thyroid gland or defect of thyroid hormone synthesis. The prevalence of CH in Korea is 1 per 4,225 people, and DUOX2 mutations were previously known as the most prevalent mutation in Korean patients with CH. This study was performed to identify the correlation between etiology and genetic mutations in patients with CH in a single tertiary hospital.

Methods: This study enrolled 26 patients (12 males and 14 females) with CH (9 ectopic thyroid, 8 dyshormonogenesis, 6 hypoplastic thyroid, 3 athyrosis) between February 2020 and April 2021. All exons and exon-intron boundary sequences of the 23 causative genes were analyzed in 26 patients by targeted next generation sequencing (NGS) panel.

Results: The median age of patients performed NGS was 10.4 years (range 3.3-22.6 years). Seventeen variants in 6 genes (DUOX2, TPO, TSHR, DUOXA2, SLC16A2 and SLC26A4) were identified in 13 patients (4 males and 9 females). DUOX2 mutations (23.5%), TPO mutations (23.5%) and TSHR mutations (23.5%) were most common detected variants in our patients. Among them, 5 patients (20%) carried biallelic mutations in DUOXA2, DUOX2, TPO and TSHR. Three compound heterozygotic mutations in DUOXA2, DUOX2, TPO and one homozygotic mutation in DUOXA2 were all found in patients with dyshormonogenesis. One compound heterozygotic mutation in TSHR was found in patient with hypoplasia. Biallelic mutations in DUOXA2 were most common (40%), which can be regarded as genetic diagnosis.

Conclusions: This study included 18 patients with thyroid gland dysgenesis and 8 patients with thyroid dyshormonogenesis. DUOX2, TPO and TSHR mutations were most common variants. The yield of genetic diagnosis using NGS panel was higher in patients with dyshormonogenesis (50%) than in patients with dysgenesis (5.6%), and DUOXA2 mutations were the most common biallelic mutations.