Ala244Val is a common, probably ancient mutation causing factor VII deficiency in Moroccan and Iranian Jews

Hannah Tamary*, Yonit Fromovich, Lea Shalmon, Ziv Reich, Orly Dym, Naomi Lanir, Benjamin Brenner, Michael Paz, Anthony S. Luder, Orit Blau, Michael Korostishevsky, Rina Zaizov, Uri Seligsohn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish
Pages (from-to)283-291
Number of pages9
JournalThrombosis and Haemostasis
Volume76
Issue number3
DOIs
StatePublished - 1996
Externally publishedYes

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