Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency.
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.
Hirschhorn
R
R
New York University Medical School, Department of Medicine, New York 10016, USA.
Yang
D R
DR
Puck
J M
JM
Huie
M L
ML
Jiang
C K
CK
Kurlandsky
L E
LE
D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D001402:B-Lymphocytes; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D016511:Severe Combined Immunodeficiency / Q000235:genetics*
D000243:Adenosine Deaminase