Molecular genetics aspects of factor XI deficiency and glanzmann thrombasthenia

Uri Seligsohn, Hava Pereti

Research output: Contribution to journalArticlepeer-review

Abstract

Factor XI deficiency and Glanzmann thrombasthenia are among the hereditary disorders frequently encountered in Israel. Factor XI deficiency is particularly frequent in Ashkenazi (Euorpean) Jews with 1:190 individuals affected by the severe deficiency and 8.1% of the population being heterozygotes. So far 4 mutations causing factor XI deficiency have been identified of which the type II (a non-sense mutation) and type III (a missense mutation) are predominant and type I and IV observed only in 5 families. Recently, the type II mutation was observed in Iraqui-Jews as well with 3.7% of 400 unrelated subjects being heterozygotes and with the type III mutation completely absent. Since Iraqui-Jews represent the original gene pool of Jews who lived in Babylon 2500 years ago we hypothesize that the type II mutation is ancient and that the type III mutation occured more recently, after the divergence of the original Babylonian Jews into Ashkenazi, Sephardic (Spanish) and Middle Eastern Jews. Preliminary data on factor XI intragenic polymorphic markers indeed indicate that type II and type III mutations reside on chromosomes each characterized by a different specific haplotype. Fifty living patients with type I Glanzmann thrombasthenia (28 families) have been observed in Israel. Most of them are Iraqui-Jewish and the rest are Arabs (5 families) and one Iranian Jewish. All Iraqui- Jewish patients have an Ilbp deletion within exon 12 of the glycoprotein (GP) Ilia resulting in a shift of the reading frame that leads to premature termination of the GPIIIa synthesis. In 3 of the Arab families a 13bp deletion was found in exon 4 of the GPIIb gene causing forced alternative splicing with 6 amino acids missing at the N-terminal region of GPIIb. For the detection of both mutations simple PCR methods were devised enabling carrier detection and prenatal diagnosis by CVS.

Original languageEnglish
Pages (from-to)81-85
Number of pages5
JournalPathophysiology of Haemostasis and Thrombosis
Volume24
Issue number2
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • Factor XI deficiency
  • Glanzmann thrombasthenia
  • Molecular genetics

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