在急性间歇性症中,HMBS基因突变和甲基比兰合成酶活性:系统性审查
Shuang Li1, Jia-Jia Lei1, Bai-Xue Dong1
1Department of the First Clinical Medical School, Shanxi Medical University, Taiyuan, China.
Medicine
|September 29, 2023
概括
急性间歇性 (AIP) 涉及HMBS基因突变,导致大多数患者的酶活性降低. 分子分析显示高异质性,误解突变是最常见的.
科学领域:
- 生物化学 生化学
- 遗传学 是一个遗传学.
- 罕见疾病 罕见疾病
背景情况:
- 急性间歇性 (AIP) 是一种罕见的遗传性疾病,由于部分缺乏甲基比兰合成酶 (HMBS),影响血红蛋白生物合成.
- 在AIP患者中,HMBS基因的突变是HMBS缺陷的根本原因.
- 关于AIP的分子流行病学研究有限,需要进一步调查HMBS基因缺陷和酶活性.
研究的目的:
- 在经典的AIP中描述HMBS基因缺陷的分子流行病学.
- 分析古典AIP患者的基甲基比兰合成酶活性水平.
- 为了将突变类型和位置与AIP中的酶活性相关联.
主要方法:
- 在PubMed,CNKI和Wang Fang数据库的系统文献搜索,截至2023年7月15日.
- 由两名审查员从15项涉及232名患者的合格研究中进行独立选择和数据提取.
- 在外周血液样本中对HMBS基因突变和红细胞HMBS活性进行统计分析.
主要成果:
- 90.5%的AIP患者表现出红细胞HMBS活性降低 (<70%).
- 确定了96种不同的HMBS突变,其中误解 (34.4%) 和拼接 (28.1%) 突变是最常见的.
- 在突变类型/位置和残留酶活性水平之间没有发现显著的关联.
结论:
- 红细胞基甲基比兰合成酶活性通常在AIP患者中减少一半,这突显了酶活性测定的诊断价值.
- AIP表现出显著的分子异质性,在不同种群中发现了像R173W和G111R这样的常见高频突变.
- 了解HMBS缺陷的分子流行病学对于有效诊断和管理AIP至关重要.
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