Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis
Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis
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DOI：
10.1210/jc.2017-02202
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发表时间：
2018-05-01
影响因子：
5.8
通讯作者：
Shi, Yufei
中科院分区：
文献类型：
--
作者：
Zou, Minjing;Alzahrani, Ali S.;Shi, Yufei
背景：先天性甲状腺功能减退症（CH）是最常见的新生儿内分泌疾病，每3000至4000名新生儿中就有一名患有CH。自1988年开始实施新生儿筛查计划以来，已发现300多例病例。目的：了解CH致病基因的突变谱，方法：采用新一代外显子组测序技术，对47个家系的55例患者进行了研究，结果：52.7%的患者存在突变（55个中的29个）在以下11个基因中：TG、TPO、DU 0X 2、SLC 26 A4、SLC 26 A7、TSHB、TSHR、NKX 2 -1、PAX 8、CDCA 8和HOX 83。在30例甲状腺激素生成障碍患者中，12例（40%）患者发现TG双等位基因突变，其次是TPO（6.7%）、SLC 26 A7（6.7%）和DUOX 2（3.3%）双等位基因突变。在2例患者中发现单等位基因SLC 26 A4突变，其中1例与SLC 26 A7中的两个串联双等位基因缺失共存。在25例甲状腺发育不全患者中，6例（24%）发现TSHR双等位基因突变。在4名不同的患者中发现一次TSHB、PAX 8、NKX 2 -1或HOX 83的双等位基因突变。在1例患者中发现单等位基因CDCA 8突变。大多数突变是新的，包括三个TG，两个TSHR，以及DUOX 2，TPO，SLC 26 A7，TSHB，NKX 2 -1，PAX 8，CDCA 8和HOX 83中各一个。SLC 26 A7和HOX 83是新的基因与甲状腺激素生成障碍和dysgenesis，either.Conclusions：TG和TSHR突变是最常见的遗传缺陷，在沙特CH患者。其他致病突变的患病率低，反映了人口的血缘性质。SLC 26 A7突变似乎与甲状腺激素生成障碍有关。
Context: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, affecting one in 3000 to 4000 newborns. Since the introduction of a newborn screening program in 1988, more than 300 cases have been identified. The underlying genetic defects have not been systematically studied.Objective: To identify the mutation spectrum of CH-causing genes.Methods: Fifty-five patients from 47 families were studied by next-generation exome sequencing.Results: Mutations were identified in 52.7% of patients (29 of 55) in the following 11 genes: TG, TPO, DUOX2, SLC26A4, SLC26A7, TSHB, TSHR, NKX2-1, PAX8, CDCA8, and HOX83. Among 30 patients with thyroid dyshormonogenesis, biallelic TG mutations were found in 12 patients (40%), followed by biallelic mutations in TPO (6.7%), SLC26A7 (6.7%), and DUOX2 (3.3%). Monoallelic SLC26A4 mutations were found in two patients, one of them coexisting with two tandem biallelic deletions in SLC26A7. In 25 patients with thyroid dysgenesis, biallelic mutations in TSHR were found in six patients (24%). Biallelic mutations in TSHB, PAX 8, NKX2-1, or HOX83 were found once in four different patients. A monoallelic CDCA8 mutation was found in one patient. Most mutations were novel, including three TG, two TSHR, and one each in DUOX2, TPO, SLC26A7, TSHB, NKX2-1, PAX8, CDCA8, and HOX83. SLC26A7 and HOX83 were novel genes associated with thyroid dyshormonogenesis and dysgenesis, respectively.Conclusions: TG and TSHR mutations are the most common genetic defects in Saudi patients with CH. The prevalence of other disease-causing mutations is low, reflecting the consanguineous nature of the population. SLC26A7 mutations appear to be associated with thyroid dyshormonogenesis.