학술논문
DUOX2variants are a frequent cause of congenital primary hypothyroidism in Thai patients
Document Type
Article
Author
Sorapipatcharoen, Kinnaree; Tim-Aroon, Thipwimol; Mahachoklertwattana, Pat; Chantratita, Wasun; Iemwimangsa, Nareenart; Sensorn, Insee; Panthan, Bhakbhoom; Jiaranai, Poramate; Noojarern, Saisuda; Khlairit, Patcharin; Pongratanakul, Sarunyu; Suprasongsin, Chittiwat; Korwutthikulrangsri, Manassawee; Sriphrapradang, Chutintorn; Poomthavorn, Preamrudee
Source
Endocrine Connections; November 2020, Vol. 9 Issue: 11 p1121-1134, 14p
Subject
Language
ISSN
20493614
Abstract
To identify the genetic etiologies of congenital primary hypothyroidism (CH) in Thai patients.CH patients were enrolled. Clinical characteristics including age, signs and symptoms of CH, pedigree, family history, screened thyroid-stimulating hormone results, thyroid function tests, thyroid imaging, clinical course and treatment of CH were collected. Clinical exome sequencing by next-generation sequencing was performed. In-house gene list which covered 62 potential candidate genes related to CH and thyroid disorders was developed for targeted sequencing. Sanger sequencing was performed to validate the candidate variants. Thyroid function tests were determined in the heterozygous parents who carried the same DUOX2or DUOXA2variants as their offsprings.There were 118 patients (63 males) included. Mean (SD) age at enrollment was 12.4 (7.9) years. Forty-five of 118 patients (38%) had disease-causing variants. Of 45 variants, 7 genes were involved (DUOX2, DUOXA2, TG, TPO, SLC5A5, PAX8and TSHR). DUOX2, a gene causing thyroid dyshormonogenesis, was the most common defective gene (25/45, 56%). The most common DUOX2variant found in this study was c.1588A>T. TGand TPOvariants were less common. Fourteen novel variants were found. Thyroid function tests of most parents with heterozygous state of DUOX2and DUOXA2variants were normal.DUOX2variants were most common among Thai CH patients, while TGandTPOvariants were less common. The c.1588A>T in DUOX2gene was highly frequent in this population.