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 VIIR variant. An intron 7 mutation, which alters the consensus donor splice site sequence, was...

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Bibliographic Details
Published in:Human genetics 1993-11, Vol.92 (5), p.446-450
Main Authors: BERNARDI, F, PATRACCHINI, P, GEMMATI, D, FERRATI, M, ARCIERI, P, PAPACCHINI, M, REDAELLI, R, BAUDO, F, MARIANI, G, MARCHETTI, G
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
coagulation factor VII
Consensus Sequence
deficiency
DNA Mutational Analysis
Factor VII Deficiency - genetics
Female
Gene Frequency
Hematologic and hematopoietic diseases
Humans
Introns
Italy
Male
man
Medical sciences
Molecular Sequence Data
mutation
Pedigree
Platelet diseases and coagulopathies
Point Mutation
polymorphism
Polymorphism, Genetic
Repetitive Sequences, Nucleic Acid
Restriction Mapping
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Summary: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 VIIR variant. An intron 7 mutation, which alters the consensus donor splice site sequence, was found in six subjects. The presence of the founder effect is suggested by their common geographical origin (a mountain 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 heterozygous condition in a subject from Northern Italy. New polymorphic alleles were detected in the repeated intron 7 region in subjects from Eastern Africa. Two missense mutations in codon 97 (Gly-->Cys, Gly-->Ser), the first found in the compound heterozygous condition with the frequent intron 7 mutation, suggest the presence of a hot spot mutation site in the second epidermal growth factor domain. Two neutral dimorphisms at codon 333Ser and 115His were detected, the last in linkage disequilibrium with the 353Arg/Gln polymorphism, and showing differences in frequency in the FVII deficient and control subjects.
ISSN:0340-6717
1432-1203
DOI:10.1007/BF00216448