在由线粒基因转换引起的表皮溶解牛皮的逆转性马赛克主义
M F Jonkman1, H Scheffer, R Stulp
1Department of Dermatology, University Hospital Groningen, The Netherlands.
Cell
|February 21, 1997
概括
转基因转化,一种反向突变,在人类中首次被证明. 这一过程解释了一般化缩良性表皮溶解牛皮的逆转性马赛克主义,提供了一种天然的基因疗法方法.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 皮肤病学 皮肤病学
背景情况:
- 泛性形良性表皮溶解 (GABEB) 是一种自体逆性基因皮肤病.
- 人类基因皮肤病中逆转性马赛克的遗传基础以前没有被确立.
- COL17A1基因突变与某些形式的表皮溶解有关.
研究的目的:
- 为了研究一个患有GABEB的患者背后的逆转性马赛克的分子机制.
- 为了证明线粒基因转换是人类细胞逆转基因突变的原因.
- 为了确定负责观察到的马赛克主义的特定遗传变化.
主要方法:
- 从受影响和未受影响的皮肤贴片中提取的患者角质细胞的DNA分析.
- 基因定型用于识别COL17A1基因中的突变.
- 失去异性分析以界定基因转换的程度.
主要成果:
- 在GABEB患者中,逆转性马赛克主义是由一个COL17A1等位基因的线粒基因转换引起的.
- 母亲的COL17A1等位基因 (1706delA) 逆转,显示在未受影响的皮肤角质细胞中失去了异性.
- 父亲的COL17A1突变 (R1226X) 在所有分析的细胞样本中仍然存在.
结论:
- 线粒基因转换在人类中起到反向突变机制的作用.
- 在GABEB中,逆转性马赛克是COL17A1基因转换的结果.
- 这种现象代表了对基因皮肤病的一种自然基因疗法的形式.
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