title: Somatic origin of inherited haemophilia A.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, University Hospital Leiden, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Bröcker-Vriends
authors.forename: E
authors.initials: E
authors.lastname: Briët
authors.forename: J C
authors.initials: JC
authors.lastname: Dreesen
authors.forename: B
authors.initials: B
authors.lastname: Bakker
authors.forename: P
authors.initials: P
authors.lastname: Reitsma
authors.forename: H
authors.initials: H
authors.lastname: Pannekoek
authors.forename: J J
authors.initials: JJ
authors.lastname: van de Kamp
authors.forename: P L
authors.initials: PL
authors.lastname: Pearson
mesh_terms: D002872:Chromosome Deletion; D002874:Chromosome Mapping; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D008297:Male; D009030:Mosaicism / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D005169:Factor VIII