SPONTANEOUS IN-VIVO REVERSION TO NORMAL OF AN INHERITED MUTATION IN APATIENT WITH ADENOSINE-DEAMINASE DEFICIENCY

Somatic mosaicism in genetic disease generally results from a de novo deleterious mutation during embryogenesis. We now describe a somatic m osaicism due to the unusual mechanism of in vivo reversion to normal o f an inherited mutation. The propositus was an adenosine deaminase-def icient (ADA(-)) child with progressive clinical improvement and unexpe ctedly mild biochemical and immunologic abnormalities. Mosaicism due t o reversion was evidenced by absence of a maternally transmitted delet erious mutation in 13/15 authenticated B cell lines and in 17% of sing le alleles cloned from blood DNA, despite retention of a maternal 'pri vate' ADA polymorphism linked to the mutation. Establishment of signif icant somatic mosaicism following reversion to normal could modify any disorder in which revertant cells have a selective advantage.