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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
1   Haematology Department, Hospital Universitario La Paz, Madrid, Spain
,
Adoración Venceslá
2   Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
María Teresa Alvárez-Román
1   Haematology Department, Hospital Universitario La Paz, Madrid, Spain
,
Isabel Rivas
1   Haematology Department, Hospital Universitario La Paz, Madrid, Spain
,
Ihosvany Fernández
1   Haematology Department, Hospital Universitario La Paz, Madrid, Spain
,
Nora Butta
1   Haematology Department, Hospital Universitario La Paz, Madrid, Spain
,
Manel Baena
2   Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Pablo Fuentes-Prior
3   Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Eduardo F. Tizzano
2   Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Víctor Jiménez-Yuste
1   Haematology Department, Hospital Universitario La Paz, Madrid, Spain
› Author Affiliations Financial support:This work was supported by Real Fundación Victoria Eugenia, Fundació Catalana d’Hemofilia and SAF2007–64140 from Ministerio de Ciencia e Innovación, Spain.
Further Information

Publication History

Received: 02 February 2010

Accepted after major revision: 14 May 2010

Publication Date:
24 November 2017 (online)

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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
 

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