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不确定的DMD误解变体的临床和遗传解释:来自mRNA和蛋白质研究的证据

Zhiying Xie¹, Chang Liu¹, Haiyan Yu²

¹Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.

Orphanet journal of rare diseases

|March 15, 2024

概括

不确定的双氨酸 (DMD) 基因误解变异的致病性解释是复杂的. 这项研究表明异常拼接可以重新分类这些变体,改善杜申肌肉发育不良症 (DMD) 和贝克尔肌肉发育不良症 (BMD) 的诊断.

科学领域:

遗传学是一个遗传学.
分子生物学分子生物学
神经肌肉疾病神经肌肉疾病

背景情况:

双氨酸 (DMD) 基因中的致病性误解变异在双氨酸病变中很少被报告.
大多数DMD误解变异的致病性仍然不确定且难以解释.
调查异常拼接对于重新评估这些变体的意义至关重要.

研究的目的:

为了确定DMD误解变体是否会导致异常拼接.
用mRNA和蛋白质研究重新解释DMD误解变异的致病性.
为了提高疑似肌痛性肌痛病的患者的诊断准确度.

主要方法:

招募了9名与血清肌酸激酶水平升高的无关患者.
进行了详细的临床,成像和病理评估.
进行了常规基因测试,以及肌肉衍生的mRNA和蛋白质研究,以检测二氨酸和糖基因.

主要成果:

常规基因检测发现了9种预测的DMD误解变体,6种新型和不确定的意义.
双氨酸mRNA研究发现3种变体导致异常拼接,导致移变体.
所有9种DMD变异都被重新分类为致病性或可能致病性,使得DMD/BMD的确切诊断成为可能.

结论:

异常拼接是看似不确定的DMD误解变体中致病性的关键机制.
肌肉活检和mRNA研究对于精确的基因解释在dystrophinopathies必不可少.
这种方法增强了杜申尼和贝克尔肌肉发育不良的临床和遗传诊断.

关键词:

在 DMD DMD 里面,你会发现这是一种异常的拼接.消极性肌肉变质症 (Dystrophinopathies) 是一种肌肉变质的疾病.错误的意义变体

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