新的WFS1变种与不同的糖尿病表型有关
Lei Wu1, Juan Zhang1, Danjie Li1
1Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Shanghai, China.
Frontiers in genetics
|September 2, 2024
概括
WFS1基因中的遗传变异与沃尔夫拉姆综合征等疾病和早期发病的糖尿病有关. 早期对WFS1变异的基因测试可以改善对内分泌网膜压力相关疾病的诊断和治疗.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- WFS1基因编码了狼胺,这对于内分泌网膜 (ER) 恒温是必不可少的.
- WFS1变种与沃尔夫拉姆综合征,糖尿病和精神疾病有关,往往导致误诊.
- 了解WFS1的作用对于诊断复杂的遗传疾病至关重要.
研究的目的:
- 为了研究WFS1基因变异在患有早期发病未分类糖尿病的患者中的作用.
- 评估已识别的WFS1化合物异质合体变体的功能影响.
- 突出WFS1变异在ER压力相关疾病中的临床意义.
主要方法:
- 在165名患有早期糖尿病的患者中进行了全外体测序 (WES).
- 变体解释遵循ACMG/AMP 2015指导方针,并通过桑格测序进行验证.
- 试验室内实验评估了WFS1化合物异构体变异体对ER应激和细胞活力的功能影响.
主要成果:
- 在两名患有沃尔夫拉姆综合征类似疾病 (WSLD) 的患者中发现了WFS1复合异构型变体 (p.A214fs*74/p.F329I和p.I427S/p.I304T).
- 这些变异增加了ER压力,降低了细胞活力,并降低了SERCA2b mRNA水平.
- 在另外三名患者中发现了致病或可能致病的WFS1异构体变体.
结论:
- 对WFS1变异的早期遗传测试对于诊断年轻发病糖尿病和WSLD至关重要.
- WFS1变异导致ER压力和细胞活力降低,影响临床结果.
- 将遗传发现纳入临床实践可以减少误诊并完善治疗策略.
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