A common ancestral mutation (C128X) occurring in 11 non-Jewish families from the UK with factor XI deficiency

被引:61
作者
Bolton-Maggs, PHB
Peretz, H
Butler, R
Mountford, R
Keeney, S
Zacharski, L
Zivelin, A
Seligsohn, U
机构
[1] Manchester Royal Infirm, Dept Clin Haematol, Manchester M13 9WL, Lancs, England
[2] Manchester Royal Infirm, Dept Mol Diagnost, Manchester M13 9WL, Lancs, England
[3] Tel Aviv Sourasky Med Ctr, Clin Biochem Lab, Tel Aviv, Israel
[4] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel
[5] Liverpool Womens Hosp, Dept Mol Genet, Liverpool, Merseyside, England
[6] VA Med Ctr, White River Jct, VT 05009 USA
[7] Dartmouth Coll Sch Med, Lebanon, NH USA
[8] Chaim Sheba Med Ctr, Amalia Biron Res Inst Thrombosis & Haemostasis, IL-52621 Tel Hashomer, Israel
[9] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
关键词
factor XI; gene mutation; founder effect;
D O I
10.1111/j.1538-7836.2004.00723.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Factor XI (FXI) deficiency is a mild bleeding disorder that is particularly common in Ashkenazi Jews, but has been reported in all populations. In Jews, two FXI gene (F 11) mutations (a stop codon in exon 5, E117X, type II, and a point mutation in exon 9, F283L, type III) are particularly common, but in other populations a variety of different mutations have been described. In the Basque region of France one mutation, C38R in exon 3, was found in eight of 12 families studied, haplotype analysis suggesting a founder effect. In the course of screening 78 unrelated individuals (including 15 Jewish and 12 Asian) we have found 10 Caucasian non-Jewish patients with the mutation C128X in exon 5. Individuals were investigated because of a personal or family history of bleeding, or finding a prolonged activated partial thromboplastin time. Individuals negative for the type II and type III Mutations were screened by a combination of SSCP and heteroduplex analysis. The C128X mutation was found in 10 families (one previously described). Among three individuals with severe FXI deficiency, one was homozygous for the C128X mutation, and two were compound heterozygotes for the C128X and another mutation other individuals were carriers of the C128X mutation. This is a nonsense mutation producing a truncated protein; individuals have FXI antigen levels concordant with FXI coagulant activity. Haplotype analysis of 11 families, including a further kindred previously reported from the USA, but which originally came from the UK (in which the index patient was homozygous for C128X), suggests a founder effect.
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页码:918 / 924
页数:7
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