title: Characterization of five partial deletions of the factor VIII gene.
abstract: Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, we have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes.
mesh_terms: D002872:Chromosome Deletion; D004262:DNA Restriction Enzymes; D005091:Exons; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D005796:Genes; D006580:Genetic Carrier Screening; D006467:Hemophilia A / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic
chemical_list: D005169:Factor VIII; D004262:DNA Restriction Enzymes