title: Clinical and genetic findings in five female patients with haemophilia A: Identification of a novel missense mutation, p.Phe2127Ser.
abstract: 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.
authors.affiliation: Haematology Department, Hospital Universitario La Paz, Madrid, Spain. monicamsalces@gmail.com
authors.forename: Mónica
authors.initials: M
authors.lastname: Martín-Salces
authors.forename: Adoración
authors.initials: A
authors.lastname: Venceslá
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Alvárez-Román
authors.forename: Isabel
authors.initials: I
authors.lastname: Rivas
authors.forename: Ihosvany
authors.initials: I
authors.lastname: Fernandez
authors.forename: Nora
authors.initials: N
authors.lastname: Butta
authors.forename: Manel
authors.initials: M
authors.lastname: Baena
authors.forename: Pablo
authors.initials: P
authors.lastname: Fuentes-Prior
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Tizzano
authors.forename: Víctor
authors.initials: V
authors.lastname: Jiménez-Yuste
mesh_terms: D000293:Adolescent; D013734:Androgen-Insensitivity Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005169:Factor VIII / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006395:Hemarthrosis; D006467:Hemophilia A / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010649:Phenylalanine / Q000235:genetics; D012694:Serine / Q000235:genetics; D012723:Sex; D035781:Siblings; D013030:Spain; D055815:Young Adult
chemical_list: D012694:Serine; D010649:Phenylalanine; D005169:Factor VIII