Abstract
Congenital afibrinogenemia (CAF) is a rare coagulation disorder characterized by very low or unmeasurable levels of functional and immunoreactive fibrinogen in plasma, associated with a hemorrhagic phenotype of variable severity. It is transmitted as an autosomal recessive trait (prevalence 1: 1,000,000) and is invariantly associated with mutations affecting one of the three fibrinogen genes (FGA, FGB, and FGG, coding for Aα, Bβ, and γ chain, respectively). Fibrinogen is secreted by hepatocytes as a hexamer composed of two copies of each chain; the lack of one chain has been demonstrated to prevent its secretion. Most genetic defects causing afibrinogenemia are point mutations, whereas only three large deletions have been identified so far, all affecting the FGA gene. We here report the molecular characterization of six unrelated afibrinogenemic patients leading to the identification of eight different mutations, four hitherto unknown: a 4.1-Kb large deletion involving exon I of FGA (AC107385:g. 65682_69828del), two nonsense mutations (p.Trp229X in FGA and p.Trp266X in FGB), and an ins-del mutation (g. 1787_1789del3ins12) in FGA. The molecular characterization of CAF-causing genetic defects increases our understanding on the genetic basis of this disease and might be helpful for prenatal screening purposes, as also demonstrated during this study.
| Original language | English |
|---|---|
| Pages (from-to) | 546-551 |
| Number of pages | 6 |
| Journal | Thrombosis and Haemostasis |
| Volume | 97 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2007 |
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Keywords
- Congenital afibrinogenemia
- Fibrinogen
- Large deletion
- Mutational screening
- Point mutations
ASJC Scopus subject areas
- Hematology
Cite this
Mutational screening of six afibrinogenemic patients : Identification and characterization of four novel molecular defects. / Monaldini, Luca; Asselta, Rosanna; Duga, Stefano; Peyvandi, Flora; Karimi, Mehran; Malcovati, Massimo; Tenchini, Maria Luisa.
In: Thrombosis and Haemostasis, Vol. 97, No. 4, 04.2007, p. 546-551.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mutational screening of six afibrinogenemic patients
T2 - Identification and characterization of four novel molecular defects
AU - Monaldini, Luca
AU - Asselta, Rosanna
AU - Duga, Stefano
AU - Peyvandi, Flora
AU - Karimi, Mehran
AU - Malcovati, Massimo
AU - Tenchini, Maria Luisa
PY - 2007/4
Y1 - 2007/4
N2 - Congenital afibrinogenemia (CAF) is a rare coagulation disorder characterized by very low or unmeasurable levels of functional and immunoreactive fibrinogen in plasma, associated with a hemorrhagic phenotype of variable severity. It is transmitted as an autosomal recessive trait (prevalence 1: 1,000,000) and is invariantly associated with mutations affecting one of the three fibrinogen genes (FGA, FGB, and FGG, coding for Aα, Bβ, and γ chain, respectively). Fibrinogen is secreted by hepatocytes as a hexamer composed of two copies of each chain; the lack of one chain has been demonstrated to prevent its secretion. Most genetic defects causing afibrinogenemia are point mutations, whereas only three large deletions have been identified so far, all affecting the FGA gene. We here report the molecular characterization of six unrelated afibrinogenemic patients leading to the identification of eight different mutations, four hitherto unknown: a 4.1-Kb large deletion involving exon I of FGA (AC107385:g. 65682_69828del), two nonsense mutations (p.Trp229X in FGA and p.Trp266X in FGB), and an ins-del mutation (g. 1787_1789del3ins12) in FGA. The molecular characterization of CAF-causing genetic defects increases our understanding on the genetic basis of this disease and might be helpful for prenatal screening purposes, as also demonstrated during this study.
AB - Congenital afibrinogenemia (CAF) is a rare coagulation disorder characterized by very low or unmeasurable levels of functional and immunoreactive fibrinogen in plasma, associated with a hemorrhagic phenotype of variable severity. It is transmitted as an autosomal recessive trait (prevalence 1: 1,000,000) and is invariantly associated with mutations affecting one of the three fibrinogen genes (FGA, FGB, and FGG, coding for Aα, Bβ, and γ chain, respectively). Fibrinogen is secreted by hepatocytes as a hexamer composed of two copies of each chain; the lack of one chain has been demonstrated to prevent its secretion. Most genetic defects causing afibrinogenemia are point mutations, whereas only three large deletions have been identified so far, all affecting the FGA gene. We here report the molecular characterization of six unrelated afibrinogenemic patients leading to the identification of eight different mutations, four hitherto unknown: a 4.1-Kb large deletion involving exon I of FGA (AC107385:g. 65682_69828del), two nonsense mutations (p.Trp229X in FGA and p.Trp266X in FGB), and an ins-del mutation (g. 1787_1789del3ins12) in FGA. The molecular characterization of CAF-causing genetic defects increases our understanding on the genetic basis of this disease and might be helpful for prenatal screening purposes, as also demonstrated during this study.
KW - Congenital afibrinogenemia
KW - Fibrinogen
KW - Large deletion
KW - Mutational screening
KW - Point mutations
UR - http://www.scopus.com/inward/record.url?scp=34247118412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247118412&partnerID=8YFLogxK
U2 - 10.1160/TH06-12-0743
DO - 10.1160/TH06-12-0743
M3 - Article
C2 - 17393016
AN - SCOPUS:34247118412
VL - 97
SP - 546
EP - 551
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 4
ER -