title: Inversion of intron 22 in isolated cases of severe hemophilia A.
abstract: Inversion involving intron 22 is the commonest type of mutation causing severe hemophilia A (HA). We investigated 15 families with isolated cases and 5 families with two or three brothers as the only affected members with hemophilia A, in order to determine the carrier status of the mothers, the origin of the mutation and the presence of germinal mosaicism. Our results show that all mothers tested were carriers of the inversion. In addition, three families whose unique hemophilic member was not available for analysis, were screened for the inversion. In one of these last families, the mother was diagnosed as a carrier and her sister and her niece as non-carriers. DNA haplotype analysis in 8 families with grandparents available for study demonstrated that the inversion originated almost exclusively in male germ cells. These findings have important relevance for genetic counselling in families with an isolated case or to exclude germinal mosaicism. Inversion analysis should constitute the first step in molecular diagnosis of severe hemophilia A.
authors.affiliation: Molecular Genetics Unit, Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: E F
authors.initials: EF
authors.lastname: Tizzano
authors.forename: M
authors.initials: M
authors.lastname: Domènech
authors.forename: M
authors.initials: M
authors.lastname: Baiget
mesh_terms: D007446:Chromosome Inversion; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D006239:Haplotypes / Q000235:genetics; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D009030:Mosaicism; D010375:Pedigree; D014960:X Chromosome
chemical_list: D005169:Factor VIII