Summary
We found a partial deletion of the clotting factor VIII gene of about 2000 bp, spanning exon 5 and part of intervening sequence 4 and 5 in an isolated patient with severe haemophilia A. The mother of the patient, who appeared to be a non-carrier on the basis of coagulation assays and restriction fragment length polymorphism analysis in the family, turned out to be a mosaic for the deletion, not only in her germ cells, but also in various somatic cells. These findings suggest that the mutation is the result of an event in early embryogenesis. If mosaicism for a mutation, either gonadal or somatic, proves to be a common phenomenon in human genetics, it is imperative to reconsider genetic risks for (future) sibs of any apparently new mutant of a hereditary disease.
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Bröcker-Vriends, A.H.J.T., Briët, E., Dreesen, J.C.F.M. et al. Somatic origin of inherited haemophilia A. Hum Genet 85, 288–292 (1990). https://doi.org/10.1007/BF00206748
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DOI: https://doi.org/10.1007/BF00206748