Jonkman M F, Scheffer H, Stulp R, Pas H H, Nijenhuis M, Heeres K, Owaribe K, Pulkkinen L, Uitto J
Department of Dermatology, University Hospital Groningen, The Netherlands.
Cell. 1997 Feb 21;88(4):543-51. doi: 10.1016/s0092-8674(00)81894-2.
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.
有丝分裂基因转换作为反向突变此前尚未在人类中得到证实。我们在此报告，一名患有常染色体隐性遗传性皮肤病——泛发性萎缩性良性大疱性表皮松解症的复合杂合先证者的回复性嵌合现象，是由两个突变的COL17A1等位基因之一的有丝分裂基因转换引起的。具体而言，在源自临床未受影响皮肤斑块的回复性角质形成细胞中，COL17A1上围绕突变位点（1706delA）的母本等位基因显示出突变回复以及至少381 bp片段上的杂合性缺失；父本突变（R1226X）在所有细胞样本中均存在。回复性嵌合现象代表了一种自然基因治疗方式。
