DUOX2 variants are a frequent cause of congenital primary hypothyroidism in Thai patients.
DUOX2 variants are a frequent cause of congenital primary hypothyroidism in Thai patients.
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DOI：
10.1530/ec-20-0411
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发表时间：
2020-11
影响因子：
2.9
通讯作者：
Poomthavorn P
中科院分区：
文献类型：
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作者：
Sorapipatcharoen K;Tim-Aroon T;Mahachoklertwattana P;Chantratita W;Iemwimangsa N;Sensorn I;Panthan B;Jiaranai P;Noojarern S;Khlairit P;Pongratanakul S;Suprasongsin C;Korwutthikulrangsri M;Sriphrapradang C;Poomthavorn P
确定泰国患者先天性原发性甲状腺功能减退症 (CH) 的遗传病因。 CH 患者被纳入。收集CH的临床特征，包括年龄、CH体征和症状、家系、家族史、促甲状腺激素筛查结果、甲状腺功能检查、甲状腺影像学、CH临床病程和治疗。通过下一代测序进行临床外显子组测序。开发了涵盖 62 个与 CH 和甲状腺疾病相关的潜在候选基因的内部基因列表，用于靶向测序。进行桑格测序以验证候选变体。在携带与其后代相同的 DUOX2 或 DUOXA2 变体的杂合父母中进行了甲状腺功能测试。共有 118 名患者（63 名男性）。入学时的平均 (SD) 年龄为 12.4 (7.9) 岁。 118 名患者中有 45 名 (38%) 存在致病变异。在 45 个变体中，涉及 7 个基因（DUOX2、DUOXA2、TG、TPO、SLC5A5、PAX8 和 TSHR）。 DUOX2 是一种导致甲状腺激素生成异常的基因，是最常见的缺陷基因（25/45，56%）。本研究中发现的最常见的 DUOX2 变体是 c.1588A>T。 TG 和 TPO 变体不太常见。发现了十四种新变体。大多数具有 DUOX2 和 DUOXA2 变异杂合状态的父母的甲状腺功能测试均正常。 DUOX2 变异在泰国 CH 患者中最常见，而 TG 和 TPO 变异不太常见。 DUOX2 基因中的 c.1588A>T 在该群体中非常频繁。
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 DUOX2 or DUOXA2 variants 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, PAX8 and TSHR). DUOX2, a gene causing thyroid dyshormonogenesis, was the most common defective gene (25/45, 56%). The most common DUOX2 variant found in this study was c.1588A>T. TG and TPO variants were less common. Fourteen novel variants were found. Thyroid function tests of most parents with heterozygous state of DUOX2 and DUOXA2 variants were normal. DUOX2 variants were most common among Thai CH patients, while TG and TPO variants were less common. The c.1588A>T in DUOX2 gene was highly frequent in this population.