title: Ala244Val is a common, probably ancient mutation causing factor VII deficiency in Moroccan and Iranian Jews.
abstract: We investigated the molecular basis for factor VII (FVII) deficiency in Israel and found that 13 patients were homozygous and 10 heterozygous for a C to T substitution at nucleotide 10648 of the FVII gene. This predicted an Ala244Val change and was associated with decreased FVII activity and antigen level. Of the 36 Ala244Val positive alleles, 20 were observed in patients of Moroccan origin, 10 in Iranian-Jewish patients and 6 in patients of other origins. A computer model of the serine protease domain of FVII suggested that the Ala244Val substitution may cause distortion of the entire protein structure. Intragenic polymorphic sites analyses disclosed a founder effect for the Moroccan and Iranian-Jewish patients. A survey of the Ala244Val mutation revealed an allele frequency of 1:42.5 in Moroccan Jews and 1:40 in Iranian Jews. As Moroccan Jews have been separated from Iranian Jews for more than two millennia, the data suggest that the Ala244Val mutation occurred in ancient times.
authors.affiliation: Pediatric Hematology Oncology Center, Schneider Children's Medical Center of Israel.
authors.forename: H
authors.initials: H
authors.lastname: Tamary
authors.forename: Y
authors.initials: Y
authors.lastname: Fromovich
authors.forename: L
authors.initials: L
authors.lastname: Shalmon
authors.forename: Z
authors.initials: Z
authors.lastname: Reich
authors.forename: O
authors.initials: O
authors.lastname: Dym
authors.forename: N
authors.initials: N
authors.lastname: Lanir
authors.forename: B
authors.initials: B
authors.lastname: Brenner
authors.forename: M
authors.initials: M
authors.lastname: Paz
authors.forename: A S
authors.initials: AS
authors.lastname: Luder
authors.forename: O
authors.initials: O
authors.lastname: Blau
authors.forename: M
authors.initials: M
authors.lastname: Korostishevsky
authors.forename: R
authors.initials: R
authors.lastname: Zaizov
authors.forename: U
authors.initials: U
authors.lastname: Seligsohn
mesh_terms: D000409:Alanine / Q000235:genetics; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000208:ethnology; D007557:Israel / Q000453:epidemiology; D007585:Jews; D009018:Morocco / Q000208:ethnology; D009154:Mutation
chemical_list: D005167:Factor VII; D000409:Alanine