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Inversion of intron is a rare cause of severe hemophilia A in Indian population

2004; Elsevier BV; Volume: 2; Issue: 8 Linguagem: Inglês

10.1111/j.1538-7836.2004.00794.x

1538-7933

Kanjaksha Ghosh, Shrimati Shetty, D. Mohanty,

Cancer-related gene regulation

We read with interest the letter by Cumming [1] on the prevalence of intron 1 inversions in severe hemophilia A cases in the United Kingdom. We studied a relatively large cohort of 241 severe hemophilia A cases and found three patients (1.24%) with this inversion [2] in contrast to the 3.75% reported by Choudhary et al. [3] on a small number of samples from the North Indian population. Another report [4] suggested that a significant proportion of this mutation might arise in patients with severe hemophilia A who have no family history. In about two thirds of the cases mutations may arise de novo in patients with severe hemophilia A who have no family history of the disease. In only one of our sporadic cases, other relevant female family members also tested positive for this inversion. As this inversion is on intron 1 and this genetic pathology produces clinically severe hemophilia phenotype, we wondered whether this pathology might be associated with the presence of totally non-functional factor (F)VIII molecules in circulation. We tested this hypothesis in all our patients using factor VIII antigen assay (Asserachrom VIII: C antigen, Diagnostica Stago, Asniers, France). All the samples positive for intron 1 inversion of FVIII gene tested negative for FVIII antigen. None of our three patients have developed inhibitors and none of them had additional pathology of inversion of intron 22, which is another important cause of severe hemophilia A all over the world. The reason we wanted to see the prevalence of inversion of intron 1 in our population was to integrate this simple PCR based technology for our carrier detection and prenatal diagnosis program [5], which now has been running successfully over the last seven years. The meager presence of 1.24% of this pathology in our severe hemophilia A population will not make it a cost-effective endeavor. However, for a single family known to harbor this mutation, this technique can be extremely useful to provide prenatal diagnosis or carrier detection for that family.