Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion
Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion
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DOI：
10.1016/s0092-8674(00)81894-2
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发表时间：
1997-02-21
期刊：
影响因子：
64.5
通讯作者：
Uitto, J
中科院分区：
文献类型：
--
作者：
Jonkman, MF;Scheffer, H;Uitto, J
有丝分裂基因转换作为反向突变在人类中尚未被证实。我们在这里报道了一例患有常染色体隐性遗传性皮肤病的复合杂合子先证者的回复嵌合体，泛发性萎缩性良性大疱性表皮松解症，是由两个突变的COL17A1等位基因中的一个有丝分裂基因转换引起的。具体地说，COL17A1(1706delA)突变位点周围的母系等位基因显示，在来自临床未受影响的皮肤斑块的逆转角质形成细胞中，突变逆转和杂合性丧失至少381bp；父系突变(R1226X)仍然存在于所有细胞样本中。逆转嵌合体代表了一种自然基因治疗的方式。
Mitotic gene conversion acting as reverse mutation has not been previously demonstrated in human. We report here that the revertant mosaicism of a compound heterozygous proband with an autosomal recessive genodermatosis, generalized atrophic benign epidermolysis bullosa, is caused by mitotic gene conversion of one of the two mutated COL17A1 alleles. Specifically, the maternal allele surrounding the mutation site on COL17A1 (1706delA) showed reversion of the mutation and loss of heterozygosity along a tract of at least 381 bp in revertant keratinocytes derived from clinically unaffected skin patches; the paternal mutation (R1226X) remained present in all cell samples. Revertant mosaicism represents a way of natural gene therapy.