A Nonsense Mutation in &lt;i&gt;FGA&lt;/i&gt; g.3807C→T (p.R159X) Causes Afibrinogenaemia in the Homozygous Form

Cappelletti, Roberto; Tersek, Y.; Ruiz-Sáez, Arlette; Meyer, Michael

doi:10.1159/000220336

Cited by 1 publication

(2 citation statements)

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“…1,4 The second variant in case 9 was FGA c.532C>T predicting the stop gain codon substitution p.Arg178* that predicts nonsense-mediated decay of the variant FGA mRNA. Homozygosity for p.Arg178* has previously been associated with afibrinogenemia, 6,7 confirming that this variant prevents expression of the fibrinogen Aα chain. Within the study pedigree, monoallelic FGA p.Arg178* was also detected in the father of the index case (case 3), who had concordant FGN-ACT (2.2 g/L)…”

Section: A S E De Scrip Ti Onmentioning

confidence: 61%

“…10 The remaining qualitative variant (case 8) was a FGB missense variant shown experimentally to alter fibrin polymerization but through an unknown mechanism. 11 The coinherited quantitative variants were either stop gains (cases 1 and 2) or were predicted to disrupt transcript splicing (cases [3][4][5][6][7][8] and in all but two cases have also been reported as homozygous traits in cases with afibrinogenemia. The eight cases had a median age of 45 years and comprised six women.…”

Section: Surve Y Of Pre VI Ous Ly Rep Orted C a Se Smentioning

confidence: 99%

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Pseudohomozygous dysfibrinogenemia

Peck

Reilly‐Stitt

Doherty

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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Essentials• Hypodysfibrinogenaemia (HD) can cause bleeding or thrombosis and is usually monoallelic.• A new case report and database search identifes a genetically distinct subtype of recessive HD.• Cases inherit qualitative and quantitative fibrinogen gene variants that are biallelic.• This disorder is better classified as pseudohomozygous dysfibrinogenemia.Heritable fibrinogen disorders have variable and overlapping clinical manifestations and are by convention subclassified according to the results of quantitative and qualitative fibrinogen testing of plasma. 1,2 According to this classification, a concordant reduction of plasma fibrinogen antigen and function indicates the disorders afibrinogenemia and hypofibrinogenemia (Online Mendelian Inheritance in Man [OMIM] No. 202400) in which there are reduced circulating levels of fibrinogen.These disorders are usually associated with variants in the fibrinogen genes FGA, FGB, or FGG that predict failure of expression or secretion of the fibrinogen polypeptide and which are usually biallelic in afibrinogenemia and monoallelic in hypofibrinogenemia. 3 In dysfibrinogenemia (OMIM No. 616004) plasma fibrinogen antigen is normal but function is reduced, usually because of an underlying monoallelic missense variant disrupting a functionally critical region of the fibrinogen polypeptide. 3,4 A further disorder termed hypodysfibrinogenemia (OMIM No. 616004) is characterized by reduced fibrinogen function but also a less marked reduction of plasma fibrinogen antigen that may arise from abnormal assembly, secretion, or increased clearance of the fibrinogen chains. 5 Here, we report a new case with a severe heritable fibrinogen disorder and review the literature to highlight that hypodysfibrinogenemia is genetically heterogeneous and includes a distinct subset of cases better classified as pseudohomozygous dysfibrinogenemia.

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Section: A S E De Scrip Ti Onmentioning

confidence: 61%