von Willebrand factor multimer composition is modified following oral methionine load in women with thrombosis, but not in healthy women.

Hyperhomocysteinemia is associated with an increased risk of venous and arterial thrombosis, probably by inducing endothelial damage. Von Willebrand factor (VWF) is an endothelial marker protein. It is a plasma multimeric molecule that plays a thrombophilic role.

Familial nonrandom inactivation linked to the X inactivation centre in heterozygotes manifesting haemophilia A.

A basic tenet of the Lyon hypothesis is that X inactivation occurs randomly with respect to parental origin of the X chromosome. Yet, nonrandom patterns of X inactivation are common - often ascertained in women who manifest recessive X-linked disorders despite being heterozygous for the mutation. Usually, the cause of skewing is cell selection disfavouring one of the cell lineages created by random X inactivation.

Small FVIII gene rearrangements in 18 hemophilia A patients: five novel mutations.

Hemophilia A (HA) is a disorder caused by mutations of the FVIII gene, which is located on the tip of the long arm of the X chromosome. In a cohort of 18 unrelated Italian patients affected with HA of varying severity, we performed mutational screening of the gene by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing of abnormal peaks. We identified five novel mutations and 9 previously reported DNA alterations.

Duplication of exon 13 causes one third of the cases of mild hemophilia A in northern Italy.

A rearrangement of exon 13 in the factor VIII gene has been identified as the causative mutation in 32% of Northern Italian patients with mild hemophilia A. We have demonstrated that all share a common haplotype, thus suggesting that the mutation likely occurred in a single ancestor. To date, no predominant mutation has been identified in mild hemophilia A, therefore it would be extremely useful to carry out more extensive studies to ascertain whether the mutation is confined to northern Italy.

Analysis of 18 novel mutations in the factor VIII gene.

We describe 18 novel mutations, unreported in the Haemophilia A mutation Databases, that have been identified in a cohort of unrelated, Italian patients affected with haemophilia A (HA). Screening of the factor VIII gene (FVIII) was performed using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. Eight mutations were characterized as non-missense alterations, and the remaining 10 were missense mutations.

Mutation analysis impact on the genetic counseling of sporadic hemophilia B families.

Previous studies have shown that hemophilia B (HB) is the result of several different mutations, mostly single nucleotide substitutions, in the factor IX (FIX) gene. In order to evaluate the impact of mutation analysis on genetic counseling in sporadic and uninformative HB familial pedigrees, we re-analyzed by the conformation sensitive gel electrophoresis (CSGE) technique 14 patients, previously studied by restriction fragment length polymorphisms (RFLPs). A single mutation was present within the FIX gene of each patient: 12 mutations were single base substitutions, 1 was a base insertion, and 1 was a four nucleotide deletion; 4/12 mutations have not been described so far.