A mutation in LMAN1 (ERGIC-53) causing combined factor V and factor VIII deficiency is prevalent in Jews originating from the island of Djerba in Tunisia

Avichai Segal, Ariella Zivelin, Nurit Rosenberg, David Ginsburg, Ofer Shpilberg, Uri Seligsohn

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Combined deficiency of factor V and factor VIII is a rare autosomal recessive bleeding disorder that is caused by mutations in the LMAN1 or MCFD2 genes. These genes encode for proteins that form a complex that takes part in the transport of factor V and factor VIII from the endoplasmlc reticulum to Golgi. Two mutations in LMAN1 have been observed in Jews: a guanine (G) insertion in exon 1 among Middle Eastern Jewish families, and a thymidlne (T) to cytosine (C) transition in intron 9 at a donor splice site among Tunisian families. For each mutation, haplotype analysis revealed a founder effect. Because all affected Tunisian families belong to an ancient Jewish community in the island of Djerba off the coast of Tunisia, we screened members of this community for the intron 9 T → C transition. Among 233 apparently unrelated individuals five heterozygotes were detected, predicting an allele frequency of 0.0107 (95% confidence interval, 0.0035-0.0248), while among 259 North African Jews none was found to carry the mutation. The prevalence of the mutation in Djerba Jews is consistent with the observation that all affected Tunisian Jewish families have origins in Djerba and with the finding of a common haplotype for the 9 + 2 T → C mutation. The G insertion in exon 1 was found in one of 245 Iraqi Jews, predicting an allele frequency of 0.0022 (95% confidence interval, 0.0001-0.0123), but in none of 180 Iranian Jews examined. In view of the relatively low frequency of the mutations in the respective populations it seems reasonable to advocate carrier detection and prenatal diagnosis only in affected families.

Original languageEnglish
Pages (from-to)99-102
Number of pages4
JournalBlood Coagulation and Fibrinolysis
Volume15
Issue number1
DOIs
StatePublished - 1 Jan 2004

Keywords

  • Combined deficiency of factors V and VIII
  • ERGIC-53
  • F5F8D
  • Factor V
  • Factor VIII
  • LMAN1 gene
  • MCFD2 gene

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