Abstract
Factor XI (FXI) deficiency is an autosomal bleeding disorder, usually posttrauma or postsurgery, characterized by reduced levels of coagulation FXI in plasma. The disease is highly prevalent in Ashkenazi Jews (heterozygote frequency, ~9%), whereas it is considered a rare condition in most populations (prevalence of the severe deficiency, 1 in 106 in the white population). So far, >190 causative mutations have been identified throughout the F11 gene. To have a global landscape of genetic variation of F11, we explored publicly available exome-based data obtained from >60 000 individuals belonging to different ethnicities (Exome Aggregation Consortium resource). This analysis revealed profound differences in heterozygote frequencies among populations (allele frequencies: African 5 0.0016; East Asian 5 0.0045; European 5 0.0036; Finnish 5 0.00030; Latino 5 0.0021; South Asian 5 0.0015), and a prevalence significantly higher than that reported so far (eg, the calculated prevalence of the severe deficiency in Europeans would be: 12.9 in 106). In addition, this analysis allowed us to evidence recurrent and ethnic-specific mutations: p.Phe223Leu in Africans (23.5% of all mutated alleles), p.Gln263X and p.Leu424CysfsX in East Asians (28.2% and 20.5%, respectively), and p.Ala412Thr in Latinos (25%).
| Original language | English |
|---|---|
| Pages (from-to) | e1-e6 |
| Journal | Blood |
| Volume | 130 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jul 27 2017 |
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ASJC Scopus subject areas
- Immunology
- Biochemistry
- Hematology
- Cell Biology
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Exploring the global landscape of genetic variation in coagulation factor XI deficiency. / Asselta, Rosanna; Paraboschi, Elvezia Maria; Rimoldi, Valeria; Menegatti, Marzia; Peyvandi, Flora; Salomon, Ophira; Duga, Stefano.
In: Blood, Vol. 130, No. 4, 27.07.2017, p. e1-e6.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Exploring the global landscape of genetic variation in coagulation factor XI deficiency
AU - Asselta, Rosanna
AU - Paraboschi, Elvezia Maria
AU - Rimoldi, Valeria
AU - Menegatti, Marzia
AU - Peyvandi, Flora
AU - Salomon, Ophira
AU - Duga, Stefano
PY - 2017/7/27
Y1 - 2017/7/27
N2 - Factor XI (FXI) deficiency is an autosomal bleeding disorder, usually posttrauma or postsurgery, characterized by reduced levels of coagulation FXI in plasma. The disease is highly prevalent in Ashkenazi Jews (heterozygote frequency, ~9%), whereas it is considered a rare condition in most populations (prevalence of the severe deficiency, 1 in 106 in the white population). So far, >190 causative mutations have been identified throughout the F11 gene. To have a global landscape of genetic variation of F11, we explored publicly available exome-based data obtained from >60 000 individuals belonging to different ethnicities (Exome Aggregation Consortium resource). This analysis revealed profound differences in heterozygote frequencies among populations (allele frequencies: African 5 0.0016; East Asian 5 0.0045; European 5 0.0036; Finnish 5 0.00030; Latino 5 0.0021; South Asian 5 0.0015), and a prevalence significantly higher than that reported so far (eg, the calculated prevalence of the severe deficiency in Europeans would be: 12.9 in 106). In addition, this analysis allowed us to evidence recurrent and ethnic-specific mutations: p.Phe223Leu in Africans (23.5% of all mutated alleles), p.Gln263X and p.Leu424CysfsX in East Asians (28.2% and 20.5%, respectively), and p.Ala412Thr in Latinos (25%).
AB - Factor XI (FXI) deficiency is an autosomal bleeding disorder, usually posttrauma or postsurgery, characterized by reduced levels of coagulation FXI in plasma. The disease is highly prevalent in Ashkenazi Jews (heterozygote frequency, ~9%), whereas it is considered a rare condition in most populations (prevalence of the severe deficiency, 1 in 106 in the white population). So far, >190 causative mutations have been identified throughout the F11 gene. To have a global landscape of genetic variation of F11, we explored publicly available exome-based data obtained from >60 000 individuals belonging to different ethnicities (Exome Aggregation Consortium resource). This analysis revealed profound differences in heterozygote frequencies among populations (allele frequencies: African 5 0.0016; East Asian 5 0.0045; European 5 0.0036; Finnish 5 0.00030; Latino 5 0.0021; South Asian 5 0.0015), and a prevalence significantly higher than that reported so far (eg, the calculated prevalence of the severe deficiency in Europeans would be: 12.9 in 106). In addition, this analysis allowed us to evidence recurrent and ethnic-specific mutations: p.Phe223Leu in Africans (23.5% of all mutated alleles), p.Gln263X and p.Leu424CysfsX in East Asians (28.2% and 20.5%, respectively), and p.Ala412Thr in Latinos (25%).
UR - http://www.scopus.com/inward/record.url?scp=85026288467&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026288467&partnerID=8YFLogxK
U2 - 10.1182/blood-2017-04-780148
DO - 10.1182/blood-2017-04-780148
M3 - Article
C2 - 28615222
AN - SCOPUS:85026288467
VL - 130
SP - e1-e6
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -