Objective Hemophilia A,an X-linked bleeding disorder,affecting 1 in 5 000 males is caused by heterogeneous mutations in factor Ⅷ gene.Inversion mutation in intron 22 of F8C gene remains its leading cause.The aim of t...Objective Hemophilia A,an X-linked bleeding disorder,affecting 1 in 5 000 males is caused by heterogeneous mutations in factor Ⅷ gene.Inversion mutation in intron 22 of F8C gene remains its leading cause.The aim of this study was to evaluate the frequency and distribution of the intron 22-inversion mutation in the patients and in the family members in the region.Methods 29 hemophilia A patients from Jammu and Kashmir(20 severe,8 moderate and 1 mild) were analyzed for intron 22-inversion mutation.Results 11(38%) were positive for the distal type of inversion mutation.The mutation was found in 9/20(45%) patients with severe factor Ⅷ deficiency and 2/8(25%) with moderate severity hemophilia A,whereas the patient with mild hemophilia A was found to be negative for inversion mutation.Evaluation of twenty-six female relatives from 11 families of inversion mutation positive patients identified one mother and one sister from one family to be the carrier,suggesting its origin in the mother. Conclusion The present study confirms the intron-22 inversion mutation in F8C gene as the major cause of hemophilia A in the population from Jammu and Kashmir with a higher frequency of inversion mutation in sporadic cases compared to the familial cases.展开更多
Objective To establish an effective laboratory examination system for carrier detection and prenatal diagnosis of haemophilia A (HA) with a variety of molecular biological methods which are simple, rapid and easy to u...Objective To establish an effective laboratory examination system for carrier detection and prenatal diagnosis of haemophilia A (HA) with a variety of molecular biological methods which are simple, rapid and easy to use. Methods Detection of inversion involving intron 22 in the FVIII gene was completed by long distance polymerase chain reaction ( PCR) and linkage analysis was performed by using several genetic polymorphisms including an intragenic Bcl I RFLP, 2 STRs and an extragenic St14 VNTR. Results Intron 22 inversion was observed in 10 out of the 21 (47.6%) pedigrees examined. Prenatal diagnosis was completed in 3 pedigrees. A further combination of the four intragenic and extragenic polymophic loci gave an informative rate of 94.7%. Conclusions Female relatives in HA families with inversion can be detected with direct diagnostic procedure. The application of long distance PCR makes the detection much more simple and rapid. For families without inversions, it is easier and more cost-effective to undertake linkage analysis of genetic polymorphism based on PCR.展开更多
文摘Objective Hemophilia A,an X-linked bleeding disorder,affecting 1 in 5 000 males is caused by heterogeneous mutations in factor Ⅷ gene.Inversion mutation in intron 22 of F8C gene remains its leading cause.The aim of this study was to evaluate the frequency and distribution of the intron 22-inversion mutation in the patients and in the family members in the region.Methods 29 hemophilia A patients from Jammu and Kashmir(20 severe,8 moderate and 1 mild) were analyzed for intron 22-inversion mutation.Results 11(38%) were positive for the distal type of inversion mutation.The mutation was found in 9/20(45%) patients with severe factor Ⅷ deficiency and 2/8(25%) with moderate severity hemophilia A,whereas the patient with mild hemophilia A was found to be negative for inversion mutation.Evaluation of twenty-six female relatives from 11 families of inversion mutation positive patients identified one mother and one sister from one family to be the carrier,suggesting its origin in the mother. Conclusion The present study confirms the intron-22 inversion mutation in F8C gene as the major cause of hemophilia A in the population from Jammu and Kashmir with a higher frequency of inversion mutation in sporadic cases compared to the familial cases.
文摘Objective To establish an effective laboratory examination system for carrier detection and prenatal diagnosis of haemophilia A (HA) with a variety of molecular biological methods which are simple, rapid and easy to use. Methods Detection of inversion involving intron 22 in the FVIII gene was completed by long distance polymerase chain reaction ( PCR) and linkage analysis was performed by using several genetic polymorphisms including an intragenic Bcl I RFLP, 2 STRs and an extragenic St14 VNTR. Results Intron 22 inversion was observed in 10 out of the 21 (47.6%) pedigrees examined. Prenatal diagnosis was completed in 3 pedigrees. A further combination of the four intragenic and extragenic polymophic loci gave an informative rate of 94.7%. Conclusions Female relatives in HA families with inversion can be detected with direct diagnostic procedure. The application of long distance PCR makes the detection much more simple and rapid. For families without inversions, it is easier and more cost-effective to undertake linkage analysis of genetic polymorphism based on PCR.
