Hirschhorn R, Yang D R, Puck J M, Huie M L, Jiang C K, Kurlandsky L E
New York University Medical School, Department of Medicine, New York 10016, USA.
Nat Genet. 1996 Jul;13(3):290-5. doi: 10.1038/ng0796-290.
Somatic mosaicism in genetic disease generally results from a de novo deleterious mutation during embryogenesis. We now describe a somatic mosaicism due to the unusual mechanism of in vivo reversion to normal of an inherited mutation. The propositus was an adenosine deaminase-deficient (ADA-) child with progressive clinical improvement and unexpectedly mild biochemical and immunologic abnormalities. Mosaicism due to reversion was evidenced by absence of a maternally transmitted deleterious mutation in 13/15 authenticated B cell lines and in 17% of single alleles cloned from blood DNA, despite retention of a maternal 'private' ADA polymorphism linked to the mutation. Establishment of significant somatic mosaicism following reversion to normal could modify any disorder in which revertant cells have a selective advantage.
遗传疾病中的体细胞嵌合现象通常源于胚胎发育过程中发生的新生有害突变。我们现在描述一种由于遗传性突变在体内异常回复至正常的机制所导致的体细胞嵌合现象。该先证者是一名腺苷脱氨酶缺陷（ADA-）患儿，临床症状逐渐改善，且生化和免疫异常出人意料地轻微。尽管保留了与该突变相关的母亲“私人”ADA多态性，但在13/15个经鉴定的B细胞系以及从血液DNA克隆的单等位基因的17%中未检测到母亲传递的有害突变，这证明了由回复突变导致的嵌合现象。回复至正常后显著体细胞嵌合现象的形成可能会改变任何其中回复细胞具有选择优势的疾病。
