ABSTRACT
OBJECTIVE: To investigate a family with factor VII (FVII) deficiency from Argentina. PATIENTS AND METHODS: The proposita is a 14-year-old girl who presented with a mild to moderate bleeding tendency. Menorrhagia is controlled with periodical administration of small doses of recombinant FVII concentrate. The mother of the proposita has a similar bleeding tendency. RESULTS: FVII activity in both patients was 20% of normal; FVII antigen was 35% of normal. Molecular biology investigation revealed that the proposita was compound heterozygote between Thr384Met and Arg413Gln. The mother had the same mutations. This was due to the fact that the father of the proposita and her maternal grandfather both carried, in spite of no relation, the same mutation, namely Arg413Gln. CONCLUSIONS: The identical defect which presented in the propositaand her mother could be explained by the genetic analysis of the father and maternal grandfather of the proposita who happened to have the same mutation (Arg413Gln).
Subject(s)
Amino Acid Substitution , Factor VII Deficiency/diagnosis , Factor VII Deficiency/genetics , Factor VII/genetics , Heterozygote , Mutation , Phenotype , Adolescent , Adult , Argentina , Blood Coagulation Tests , DNA Mutational Analysis , Factor VII Deficiency/blood , Factor VIIa/administration & dosage , Female , Genetic Association Studies , Humans , PedigreeABSTRACT
The prevalence of factor VII (FVII) deficiency in 267 Brazilian patients was estimated to be 4.1%, including one patient with significant bleeding, five with minor bleeding and five patients asymptomatic. Only one novel mutation 8926G <-- T (I140S) was seen in one patient. The other mutations were 10828G <-- A (R304Q) in three patients, 10846G <-- T (C310F) in one patient, and 10909G <-- A (G331D) in one patient. Except for one homozygous patient (C310F) with a severe deficiency, only one allele was affected in all other instances. An inverse association between F7 polymorphisms and FVII activity were found in these patients, as those with higher levels of FVII activity presented the genotype described in the literature as related to reduced FVII activity. As the R304Q mutation was the most frequent in these patients, and may be associated with an asymptomatic form of the disease, particularly in Blacks, we examined this mutation and FVII activity in 49 Blacks and 49 Caucasian blood donors with no clinical bleeding. None of the individuals showed the R304Q mutation, and FVII activity was normal in all of them, thus indicating that FVII deficiency is not common in normal individuals of these two ethnic groups in Brazil. This is the first study in South America to examine the prevalence and molecular basis of FVII deficiency, including the description of a novel mutation.
Subject(s)
Factor VII Deficiency/epidemiology , Factor VII/genetics , Adolescent , Adult , Brazil/epidemiology , Child , Child, Preschool , Factor VII Deficiency/ethnology , Factor VII Deficiency/genetics , Female , Genotype , Hemorrhage , Humans , Male , Molecular Epidemiology , Mutation, Missense , Phenotype , Point Mutation , PrevalenceSubject(s)
Blood Coagulation Disorders/therapy , Amino Acid Sequence , Animals , Blood Coagulation Disorders/genetics , Blood Coagulation Factors/genetics , Blood Coagulation Factors/immunology , Blood Coagulation Factors/therapeutic use , Clinical Trials as Topic , Cricetinae , Disease Models, Animal , Dog Diseases/genetics , Dog Diseases/therapy , Dogs , Factor VII Deficiency/genetics , Factor VII Deficiency/therapy , Hemophilia A/genetics , Hemophilia A/immunology , Hemophilia A/therapy , Hemophilia A/veterinary , Hemophilia B/genetics , Hemophilia B/therapy , Humans , Isoantibodies/biosynthesis , Isoantibodies/immunology , Molecular Sequence Data , Recombinant Proteins/immunology , Recombinant Proteins/therapeutic use , von Willebrand Diseases/diagnosis , von Willebrand Diseases/genetics , von Willebrand Diseases/therapyABSTRACT
Se encontró deficiencia combinada de los factores V y VII de la coagulación de los miembros de una femilia originaria de Espinal, Oxaca, en el Istmo de Tehuantepec. Los padres son consanguíneos, y ambos tienen el apellido Toledo. Hay labio leporino en el padre y un hijo. Ningún familiar tiene hemorragias anormales pero sus estudios de coagulación del tiempo de protrombina y de tromboplastina parcial resultaron prologados. El padre es deficiente en factor V, la madre en factor VII, y sus hijos heredaron ambas deficiencias (V y VII), lo que indica una transmisión autosómica dominante y el patrón del estado heterocigoto. Esta deficiencia no se ha descrito previamente, por lo que cabe reconocerla con el nombre Toledo-Tehuantepec