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生殖线功能丧失PAM变体在患有下垂体过分分泌的受试者中得到了丰富
Giampaolo Trivellin1,2, Adrian F Daly3, Laura C Hernández-Ramírez4,5
1Department of Biomedical Sciences, Humanitas University, Milan, Italy.
丁糖氨酸a-amidating monooxygenase (PAM) 基因中的遗传变异与垂体腺瘤和激素失衡有关. 这一发现为下垂体功能障碍提供了新的治疗点.
科学领域:
- 内分泌学 在内分泌学.
- 人类遗传学 人类遗传学
- 分子生物学分子生物学
背景情况:
- 垂体腺瘤 (PAs) 是常见的瘤,通常缺乏已知的遗传原因,导致荷尔蒙失调.
- 类甘油a-amidating单氧化酶 (PAM) 蛋白对于分泌的C端化至关重要.
研究的目的:
- 调查PAM基因在垂体腺瘤发展中的作用.
- 为了识别与下垂体功能过高相关的PAM遗传变异.
主要方法:
- 使用生殖系和瘤测序对299名零星PA患者和17名家族PA亲属进行PAM变异的查.
- 进行了生殖系拷贝数变异 (CNV) 分析.
- 检测到的单核酸变体 (SNVs) 在体外功能测试对蛋白质表达,贩运,拼接和化活性的影响.
主要成果:
- 在患有生长激素过量,儿科库辛病和其他PA的个体中,发现了7种异合体,可能是致病性PAM SNV.
- 实验室功能测定证实了这些SNVs对PAM蛋白表达和/或功能的有害影响.
- 对英国生物库外体的分析证实了PAM基因,罕见的PAMSNV和垂体功能过度之间存在显著的关联.
结论:
- 帕姆基因是一种与垂体腺体过分分泌相关的新型候选基因.
- 准PAM功能是对 pituitary高功能障碍的潜在治疗策略.
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