鉴定并研究一名患有先天性甲状腺功能减退症且甲状腺正常大小的儿童中两种新的双氧化酶 2 (DUOX2) 突变的功能。
Identification and functional studies of two new dual-oxidase 2 (DUOX2) mutations in a child with congenital hypothyroidism and a eutopic normal-size thyroid gland.
机构信息
Dipartimento di Endocrinologia e Metabolismo, Centro Eccellenza AmbiSEN, Università di Pisa, 56124 Pisa, Italy.
出版信息
J Clin Endocrinol Metab. 2009 Nov;94(11):4309-14. doi: 10.1210/jc.2009-0426. Epub 2009 Sep 29.
CONTEXT
Some cases of congenital hypothyroidism (CH) are associated with a gland of normal size.
OBJECTIVE
To explore the cause of organification defect in one child with CH and a eutopic thyroid gland, genetic analyses of TPO, DUOX2, and DUOXA2 genes were performed.
PATIENT
One child with CH, a eutopic thyroid gland, and a partial organification defect was shown after (123)I scintigraphy and perchlorate test.
METHODS
In the child with the organification defect, TPO, DUOX2, and DUOXA2 genes were analyzed. The functional activity of the DUOX2 mutants was studied after expression in eukaryotic cells.
RESULTS
No TPO or DUOXA2 gene mutations were identified. Direct sequencing of the DUOX2 gene revealed a compound heterozygous genotype for S911L and C1052Y substitutions. S911L and C1052Y caused a partial defect in H(2)O(2) production after transient expression in HeLa cells.
CONCLUSIONS
We performed a genetic analysis in one child with CH and a eutopic thyroid gland. Two new mutations in DUOX2 gene responsible for the partial deficit in the organification process were identified.
背景
一些先天性甲状腺功能减退症（CH）病例与正常大小的腺体有关。
目的
探讨 1 例 CH 伴甲状腺正常且存在部分碘化缺陷患儿的发病原因，对其甲状腺过氧化物酶（TPO）、双氧化酶 2（DUOX2）和双氧化酶辅助因子 2（DUOXA2）基因进行了遗传分析。
患者
（123）I 闪烁扫描和高氯酸盐试验显示，1 例 CH 伴甲状腺正常且存在部分碘化缺陷的患儿。
方法
对碘化缺陷患儿进行 TPO、DUOX2 和 DUOXA2 基因分析。在真核细胞中表达后，研究 DUOX2 突变体的功能活性。
结果
未发现 TPO 或 DUOXA2 基因突变。DUOX2 基因的直接测序显示 S911L 和 C1052Y 取代的复合杂合基因型。S911L 和 C1052Y 导致瞬时转染 HeLa 细胞后 H2O2 产生部分缺陷。
结论
我们对 1 例 CH 伴甲状腺正常的患儿进行了基因分析。在 DUOX2 基因中发现了两个新的突变，导致碘化过程中出现部分缺陷。
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