MOLECULAR ANALYSIS OF FACTOR-VII DEFICIENCY IN ITALY - A FREQUENT MUTATION (FVII-LAZIO) IN A REPEATED INTRONIC REGION

Molecular defects and polymorphic haplotypes of coagulation factor VII gene were studied in eight unrelated Italian subjects with factor VII deficiency, seven having the factor VII- variant, one the factor VII( R) variant. An intron 7 mutation, which alters the consensus donor spl ice site sequence, was found in six subjects. The presence of the foun der effect is suggested by their common geographical origin (a mountai n area in the Lazio region) and by the identical polymorphic haplotype underlying the mutation. A different mutation, also located in the 5' monomer of the repeated intron 7 sequence, was found in the heterozyg ous condition in a subject from Northern Italy. New polymorphic allele s were detected in the repeated intron 7 region in subjects from Easte rn Africa. Two missense mutations in codon 97 (Gly --> Cys, Gly--> Ser ), the first found in the compound heterozygous condition with the fre quent intron 7 mutation, suggest the presence of a hot spot mutation s ite in the second epidermal growth factor domain. Two neutral dimorphi sms at codon 333Ser and 115His were detected, the last in linkage dise quilibrium with the 353Arg/Gln polymorphism, and showing differences i n frequency in the FVII deficient and control subjects.