由于多种DUOX2变异的先天性甲状腺功能低下的分子和临床特征
Erika Uehara1,2, Kiyomi Abe3,4, Kanako Tanase-Nakao1
1Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
概括
这项研究扩展了DUOX2基因中已知的突变,这是先天性甲状腺功能低下症 (CH) 的关键原因. 它显示,患有多种DUOX2变异的患者往往有过渡性CH,并且在停止治疗后可能出现复发性甲状腺功能低下症.
科学领域:
- 遗传学和分子生物学
- 内分泌学 在内分泌学.
- 儿科医学 儿科医学
背景情况:
- 先天性甲状腺功能低下症 (CH) 通常是由DUOX2基因的突变引起的.
- 全方位的DUOX2变体及其在CH的临床影响仍然不完全理解.
研究的目的:
- 研究与多种致病性DUOX2变体相关的CH的分子特征和长期临床结果.
- 在CH患者中扩大DUOX2已知的突变谱.
主要方法:
- 对255名CH患者进行11个已知的CH致病基因的罕见变异的查.
- 基于蛋白质结构和残留活性对DUOX2变体进行分类,并对功能不明的变体进行体外测试.
- 对患有多种致病性DUOX2变异的患者的临床分析,包括家族分析和测序以确认异性.
主要成果:
- 在63名患者中确定了24种致病性DUOX2变异 (包括3种新型错误和1种框架转移);21名患者有多种致病性DUOX2变异,没有其他基因缺陷.
- 在不同的DUOX2变体组合 (无形/无形,无形/无形,无形/无形) 中,没有发现临床严重性的显著基因型-表型相关性.
- 已经证明,患有多种致病性DUOX2变异的患者有复发性甲状腺功能低下的风险,即使在长时间无药时隔后.
结论:
- 这项研究扩大了在先天性甲状腺功能低下症中已知的DUOX2突变格局.
- 患有多种致病性DUOX2变异的患者通常存在过渡性CH,并且复发性甲状腺功能低下症是一个显著的风险.
- 这些发现强调了这些患者长期监测的重要性.
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