Rationale: Hemophilia A is an X-linked recessive bleeding disorder caused by a deficiency or dysfunction of factor VIII (FVIII), affecting approximately 1 in 5,000 males globally, including those in northern India.Accurate carrier detection is vital for genetic counseling and early diagnosis.This study aimed to assess the allele frequencies of three key intronic polymorphisms-IVS7-SNP (G/A), rs4898352 (T/A) in intron 18 (Bcl-I), and rs4074307 (C/T) in intron 19 (Hind-III)-in Indian children with Hemophilia A and evaluate their utility in carrier detection and linkage analysis.Methods: A total of 205 unrelated male children with Hemophilia A, representing 195 families from Eastern and Northern-Central India were included.Diagnosis was confirmed via FVIII assay.Genomic DNA was extracted from peripheral leukocytes.Genotyping of the three selected intronic polymorphisms in the F8 gene was carried out using ARMS-PCR.Results: The positive allele frequencies observed for IVS7-SNP, Bcl-I, and Hind-III were 0.10, 0.53, and 0.36, respectively.The negative allele of IVS7-SNP was found to be more prevalent among affected siblings.Family histories frequently revealed multiple affected individuals and hemophilia-related deaths, emphasizing the hereditary burden of the disorder in these regions. Conclusion:The distribution of the studied polymorphisms is consistent with global heterozygosity patterns and underscores their potential role in carrier screening and linkage analysis.These findings provide a feasible genetic tool for early diagnosis and counseling in Hemophilia A, particularly in low-resource settings where direct mutation analysis is limited.
Hemaliya et al. (Mon,) studied this question.