Clinical and genetic findings in five female patients with haemophilia A: Identification of a novel missense mutation, p.Phe2127Ser

Mónica Martín-Salces; Adoración Venceslá; María Teresa Alvárez-Román; Isabel Rivas; Ihosvany Fernández; Nora Butta; Manel Baena; Pablo Fuentes-Prior; Eduardo F. Tizzano; Víctor Jiménez-Yuste

doi:10.1160/TH10-02-0085

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(04): 718-723
DOI: 10.1160/TH10-02-0085

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Clinical and genetic findings in five female patients with haemophilia A: Identification of a novel missense mutation, p.Phe2127Ser

Mónica Martín-Salces

¹Haematology Department, Hospital Universitario La Paz, Madrid, Spain

,

Adoración Venceslá

²Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

,

María Teresa Alvárez-Román

¹Haematology Department, Hospital Universitario La Paz, Madrid, Spain

,

Isabel Rivas

¹Haematology Department, Hospital Universitario La Paz, Madrid, Spain

,

Ihosvany Fernández

¹Haematology Department, Hospital Universitario La Paz, Madrid, Spain

,

Nora Butta

¹Haematology Department, Hospital Universitario La Paz, Madrid, Spain

,

Manel Baena

²Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

,

Pablo Fuentes-Prior

³Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

,

Eduardo F. Tizzano

²Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

,

Víctor Jiménez-Yuste

¹Haematology Department, Hospital Universitario La Paz, Madrid, Spain

› Author Affiliations

Abstract

Summary

Severe manifestations of X-linked recessive disorders such as haemophilia A (HA) are rare in females. Here we describe the clinical and genetic findings in five female HA patients from two different Spanish families. Three sisters born to consanguineous parents presented moderate bleeding due to a known mutation (p.Ser1791Pro) detected in a homozygous state. In the second family, two sisters with Morris syndrome (46,XY) and mild/moderate illness were hemizygous for a novel missense mutation, p.Phe2127Ser. The mutation is predicted to impair binding to the factor VIII (FVIII) carrier protein, von Willebrand factor, and thus increased clearance of FVIII from plasma. Clinical and molecular characterisation of these patients is essential to optimise follow-up, genetic counselling and treatment of the disease.

Keywords

Haemophilia A - females - F8 gene - mutations - von Willebrand factor

Full Text

References

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