title: Female haemophiliac homozygous for the factor VIII intron 22 inversion mutation, with transcriptional inactivation of one of the factor VIII alleles.
abstract: Phenotypic expression of X-linked recessive disorders, including haemophilia A, is rare in females. This report describes a female with sporadic severe haemophilia A. The female patient and her family members were evaluated by coagulation assays. Visible detectable disturbance of X chromosome structure or number, as well as 2N von Willebrand disease, were excluded as possible explanations of the haemophilia A phenotype. Molecular studies, factor VIII (FVIII) intron 22 inversion mutation analysis showed that the severe haemophilia A phenotype is the result of a maternally inherited, distal, FVIII gene inversion and a paternally inherited de novo, also distal, FVIII gene inversion. Furthermore, comparative single-stranded conformation polymorphism analysis revealed the absence of detectable maternally inherited abnormal FVIII gene transcript in the patient's peripheral blood lymphocytes. X chromosome methylation analysis indicates that this could be explained by preferential inactivation of the maternally inherited X chromosome carrying the distal FVIII gene inversion.
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa, Portugal. dezso.david@insa.min-saude.pt
authors.forename: D
authors.initials: D
authors.lastname: David
authors.forename: S
authors.initials: S
authors.lastname: Morais
authors.forename: C
authors.initials: C
authors.lastname: Ventura
authors.forename: M
authors.initials: M
authors.lastname: Campos
mesh_terms: D000483:Alleles; D004303:Dosage Compensation, Genetic; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D005169:Factor VIII