Type 2N VWD: Conclusions from the Spanish PCM-EVW-ES project
Por:
Perez-Rodriguez, A, Batlle, J, Pinto, JC, Corrales, I, Borras, N, Garcia-Martinez, I, Cid, AR, Bonanad, S, Parra, R, Mingot-Castellano, ME, Navarro, N, Altisent, C, Perez-Montes, R, Moreto, A, Herrero, S, Soto, I, Mosteirin, NF, Jimenez-Yuste, V, Jacob, AD, Fontanes, E, Mateo, J, Quismondo, NC, Batlle, F, Vidal, F, Lopez-Fernandez, MF
Publicada:
1 nov 2021
Ahead of Print:
1 sep 2021
Resumen:
Introduction Type 2N von Willebrand disease (VWD) is characterized by a decreased affinity of von Willebrand factor (VWF) for factor VIII (FVIII). Abnormal binding of FVIII to VWF (VWF:FVIIIB), results in low FVIII plasma levels, which can lead to a misdiagnosis of mild haemophilia A. Accurate diagnosis of type 2N VWD is essential for appropriate genetic counselling and therapy. This disease can be distinguished from haemophilia A by in vitro assays (measurement VWF:FVIIIB activity) and/or genetic analysis. Aim To identify the current challenges in the diagnosis and treatment of this type of VWD and provide an in-depth description of the phenotypes and mutations identified. Results Twenty-eight patients had at least one type 2N mutation, and 13 of these had a type 2N mutation combined with other variations. Three type 2N mutations were detected: p.Arg816Trp, p.Arg854Gln, and p.Arg763Ser. Two of these are the most frequently described mutations worldwide. This mutational spectrum differs from the broad spectrum seen in neighbouring France, where at least eight distinct 2N mutations have been found. In the PCM-EVW-ES cohort, 11 asymptomatic type 2N carriers with borderline FVIII plasma levels would probably have been excluded if the evaluation had been based on clinical and laboratory data only. Likewise, three patients with a severe phenotype would have been classified as homozygous for a 2N mutation if only the phenotype study had been performed. Conclusion The high detection yield and affordability of next-generation sequencing support the use of this technology as a first-line diagnostic tool in this setting.
Filiaciones:
Perez-Rodriguez, A:
INIBIC, Complex Hosp Univ A Coruna, La Coruna, Spain
Batlle, J:
INIBIC, Complex Hosp Univ A Coruna, La Coruna, Spain
Pinto, JC:
INIBIC, Complex Hosp Univ A Coruna, La Coruna, Spain
Corrales, I:
Banc Sang & Teixits BST, Haematol Serv, Barcelona, Spain
Univ Autonoma Barcelona VHIR UAB, Vall dHebron Inst Recerca, Barcelona, Spain
Borras, N:
Banc Sang & Teixits BST, Haematol Serv, Barcelona, Spain
Univ Autonoma Barcelona VHIR UAB, Vall dHebron Inst Recerca, Barcelona, Spain
Garcia-Martinez, I:
Banc Sang & Teixits BST, Haematol Serv, Barcelona, Spain
Univ Autonoma Barcelona VHIR UAB, Vall dHebron Inst Recerca, Barcelona, Spain
Cid, AR:
Hosp Univ & Politecn La Fe, Haematol Serv, Valencia, Spain
Bonanad, S:
Hosp Univ & Politecn La Fe, Haematol Serv, Valencia, Spain
Parra, R:
Univ Autonoma Barcelona VHIR UAB, Vall dHebron Inst Recerca, Barcelona, Spain
Hosp Univ Vall dHebron, Haematol Serv, Barcelona, Spain
Mingot-Castellano, ME:
Hosp Reg Univ Malaga, Haematol Serv, Malaga, Spain
Navarro, N:
Hosp Univ Dr Negrin, Haematol Serv, Las Palmas Gran Canaria, Spain
Altisent, C:
Hosp Univ Vall dHebron, Haematol Serv, Barcelona, Spain
Perez-Montes, R:
Hosp Univ Marques de Valdecilla, Haematol Serv, Santander, Spain
Moreto, A:
Hosp Univ Cruces, Haematol Serv, Baracaldo, Spain
Herrero, S:
Hosp Univ Guadalajara, Haematol Serv, Guadalajara, Spain
Soto, I:
Hosp Univ Cent Asturias, Haematol Serv, Oviedo, Spain
Mosteirin, NF:
Hosp Univ Miguel Servet, Haematol Serv, Zaragoza, Spain
Jimenez-Yuste, V:
Hosp Univ La Paz, Haematol Serv, Madrid, Spain
Jacob, AD:
Complex Hosp Univ Santiago de Compostela, Haematol Serv, Santiago, Spain
Fontanes, E:
Hosp Univ Lucus Augusti, Haematol Serv, Lugo, Spain
Mateo, J:
Hosp Sta Creu & St Pau, Haematol Serv, Barcelona, Spain
Quismondo, NC:
Hosp Univ 12 Octubre, Haematol Serv, Madrid, Spain
Batlle, F:
Lapisoft Projects SA, Haematol Serv, La Coruna, Spain
Vidal, F:
Banc Sang & Teixits BST, Haematol Serv, Barcelona, Spain
Univ Autonoma Barcelona VHIR UAB, Vall dHebron Inst Recerca, Barcelona, Spain
CIBER Enfermedades Cardiovasc CIBERCV, Haematol Serv, Madrid, Spain
Lopez-Fernandez, MF:
INIBIC, Complex Hosp Univ A Coruna, La Coruna, Spain
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