Identification of 123 previously unreported mutations in the F8 gene of Iranian patients with haemophilia A.

In Haemophilia A (HA), the deficiency in coagulation factor VIII is caused by mutations in the F8 gene. In the past, HA carrier detection in Iran used to be carried out by tracking polymorphic DNA markers - a technical strategy with poor efficacy and accuracy. For some 10 years, however, mutations have been identified by direct DNA sequencing at the Iranian Comprehensive Haemophilia Care Centre (ICHCC), resulting in the detection of 580 different mutations and accurate carrier detection. The aim of this study was to characterize and report the unreported mutations not recorded in the F8 HAMSTeRS database and HGMD, which we have detected amongst all the mutations hitherto identified. After excluding introns 1 and 22 inversions, direct DNA sequencing was used to detect mutations among our patients. These were then confirmed in another affected relative or obligate carrier. Severe cases of HA, where no mutation could be identified, were further investigated by the MLPA method. The new, unreported mutations identified include: 51 missense, 15 nonsense, 45 frame-shifts, 11 splice-site, 1 duplications. We report a large spectrum of mutations identified in the course of the past 10 years at the ICHCC, which offers this service to all patients from regions throughout Iran. Aside from the common introns 1 and 22 inversions, this work demonstrates a high degree of heterogeneity in F8 mutations. The establishment of a comprehensive Iranian HA database will improve the care and genetic counselling of Iranian HA families.

How to deal with medical and social aspects of bleeding disorders--preparing women and the family in developing countries.

There is a considerable number of women with inherited bleeding disorders in Iran. von Willebrand disease, Glanzman thrombasthenia and factor XIII deficiency are the most common coagulation disorders. The main cause of this high rate of coagulation disorders is attributed to a high rate of consanguineous marriages in Iran. Medical care continues to improve for individuals affected with coagulation disorders in Iran. However, these disorders continue to have a significant impact on the affected Iranian women. As a result of the hereditary nature of these disorders, the impact extends to the psychosocial dimension of the lives of the women. Therefore it is recommended that women with coagulation disorders are provided with psychological and social support along with coagulation therapy.

Seven novel point mutations in the F11 gene in Iranian FXI-deficient patients.

Factor XI (FXI) deficiency disorder is caused by defects in the F11 gene. The affected patients may suffer unexpected and major bleeding after trauma. Hence, the aim of this study was to identify the mutations underlying FXI deficiency in Iranian patients. The genetic basis of FXI deficiency was investigated in nine Iranian patients from unrelated families using conformation-sensitive gel electrophoresis (CSGE) and direct sequencing. Nine different mutations were detected among which seven changes were not previously reported. Among the novel mutations, one was a point mutation that interfered with normal splicing of the mRNA; the other six changes were missense mutations that resulted in amino acid substitutions. Five mutations out of nine were heterozygous and were found in moderately affected patients, whereas the other four changes were homozygous among severely affected patients.