Molecular basis and bleeding manifestations of factor XI deficiency in 11 Turkish families

Abstract

Factor XI (FXI) deficiency is an autosomal bleeding disorder characterized by variable bleeding tendency. In the present study, the gene encoding FXI (F11) was analyzed by direct sequencing in 33 individuals belonging to 11 unrelated Turkish families, and the bleeding tendency was quantitatively assessed by means of a bleeding questionnaire in 27 individuals with low FXI clotting activity and/or mutated F11 gene. We identified 10 distinct mutations (five missense, three nonsense and two splice site), four of which were novel. No mutation was found in one family. Of the four novel mutations, homozygosity for a c.89T>C (p.Phe30Ser) mutation and compound heterozygosity for a c.646G>A (p.Asp216Asn) mutation with the known c.403G>T (p.Glu135) type II Jewish mutation were associated with severe deficiency, whilst heterozygosity for the novel c.1655A>C (p.His552Arg) and c.1627G>A (p.Glu543Lys) mutations was associated with partial deficiency. p.Glu135 was found in 19% (5/27) of the mutated alleles. Bleeding score was positive in 57% (4/7) of individuals with severe and 39% (7/18) of those with partial deficiency. It was significantly correlated with clinical severity of bleeding (r = 0.43, P = 0.02), but not with FXI clotting activity (P > 0.05). There was no optimal cut-off level of the bleeding score that could predict FXI deficiency. We conclude that the spectrum of mutations found in this study reflects the genetic heterogeneity of FXI deficiency in the Turkish population. Quantitative assessment of the bleeding symptoms by a bleeding questionnaire seems to be useful for evaluating the severity of bleeding episodes, but it can not be recommended as a screening tool for FXI deficiency.

Molecular investigation of 41 patients affected by coagulation factor XI deficiency

“…Of note, we evidenced that the type-III mutation is significantly less frequent in the Italian cohort of FXI-deficient patients in comparison with the type-II mutation. This trend was previously reported both in Italian and in Turkish patients 6,7 and is quite different from that originally observed in Ashkenazi Jewish FXI-deficient patients (allele frequencies: 40.4% and 35.8%…”

Therapeutic plasma exchange for perioperative management of patients with congenital factor XI deficiency

“…However, the increasingly common preoperative coagulation screen testing indicates a greater‐than‐expected incidence . In addition, genetic mutations causing FXI deficiency have been reported in groups of other Middle East, Far East, and white ethnicities . Hence, it is not surprising that slightly more than one‐half of the patients in our series had no known Jewish ancestry, and many cases of FXI deficiency were discovered during preoperative work‐up.…”

“…The patient with a BS of 8 underwent a nonmajor procedure. The median BS for the other patients receiving FFP was 7 (range, [3][4][5][6][7][8][9][10][11][12][13], and the median FXI:C was 33% (range, 6-49%).…”

Molecular heterogeneity of factor XI deficiency in Tunisia

“…Another study performed among Italian patients evidenced a significant frequency 35.48% (11/31) of the type II nonsense mutation [19]. In addition, in two studies investigating genetic basis of FXI deficiency in Turkish [20] and Southern Iranian patients [21], this mutation accounts for 19% (5/26) and 20% (1/5), respectively whereas, only 10% (1/10) of mutated alleles was previously reported in a cohort of 10 Indian patients [22]. To the best of our knowledge, E117X is being reported here for the first time in Tunisia.…”