Twenty two novel mutations of the factor VII gene in factor VII deficiency

Factor VII is a vitamin K-dependent coagulation protease essential for the initiation phase of normal hemostasis. The human factor VII gene (FVII, als o known as F7) spans 13 kb and is located on chromosome 13, 2.8 kb upstream of the factor X gene. In the Greifswald FVII deficiency study the molecula r basis for inherited factor VII was investigated. All exons, exon-intron b oundaries and the promotor of the FVII gene were amplified by PCR and direc tly sequenced. 87 unrelated probands with reduced or low FVII activities we re investigated. Thirty-four different FVII gene lesions were analyzed in 1 01 FVII alleles of 77 unrelated probands. Twenty-two of these FVII gene les ions are novel FVII variations. The 34 different lesions comprise 31 point mutations and three small deletions. A transition in the CpG doublet accoun ted for 12 of the 34 different mutants. Sixteen mutations were noted only o nce. The missense mutation A294V and the double mutation A294V; 11128delC i n exon 8 were by far the most common mutations found in this study. The hap lotype of the different mutant FVII alleles were analyzed using six polymor phisms of the FVII gene. The haplotypes were identified in 29 mutant FVII a lleles. Five different haplotypes are linked to the mutant FVII alleles. Ex cept for one, the same haplotype was detected in FVII genes with an identic al FVII gene mutation. Different haplotypes were identified in two patients with the mutant allele A206T. It is likely that identical mutant FVII alle les with the same haplotype share the same origin. Hum Mutat 15:489-496, 20 00. (C) 2000 Wiley-Liss, Inc.