Premium
A recurrent missense mutation (Arg → Gln) and a partial deletion in factor VIII gene causing severe haemophilia A
Author(s) -
Bernardi F.,
Volinia S.,
Patracchini P.,
Gemmati D.,
Boninsegna S.,
Schwienbacher C.,
Marchetti G.
Publication year - 1989
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1989.tb04266.x
Subject(s) - exon , missense mutation , haemophilia a , gene , genetics , mutation , microbiology and biotechnology , biology , coding region , haemophilia , gene mutation , single strand conformation polymorphism , oligonucleotide
Summary The presence of gene lesions in coagulation factor VIII (FVIII) gene was investigated in 70 Italian patients severely affected by haemophilia A. cDNA probes specific for exons 14–26 of the FVIII gene were used. In two related patients a gene deletion removes exon 26, a gene lesion similar to that described previously in a British haemophiliac. In exon 24 a C to T transition in the reverse complement strand causes a missense mutation in the coding strand (CGA → CAA, 2209 Arg → Gln). The mutation is located in a very conserved FVIII homology region and severely reduces FVIII activity. By restriction analysis and hybridizations with oligonucleotide probes this gene alteration was found in two unrelated haemophiliacs and in their relatives.