Haemophilia A is an X-linked inherited bleeding disorder. Linkage diagnosis using polymorphic markers in the factor VIII gene is used to archive the carrier detection and prenatal diagnosis. The objective of this study was to establish the allele frequency and heterozygosity rate (HR) of two new intragenic markers (Intron 1 and 24) and other markers (Intron 13 and 22) using fluorescent PCR. Five hundred unrelated healthy women were screened and haemophilic family was studied for carrier detection and prenatal diagnosis. We observed five different alleles of Intron 1, 10 of Intron 24, nine of Intron 13 and six of Intron 22. The observed HR for Intron 1, 24, 13 and 22 were 34.0, 35.2, 53.0 and 42.6%, while the expected HR were 33.6, 36.3, 50.1 and 44.3%, respectively. Heterozygosity rate with the combined use of all four intragenic markers was 76.6% (383/500). In prenatal diagnosis of a haemophilic family, a pregnant woman was heterozygous with three intragenic (Intron 1, 13 and 22) and one extragenic St14 VNTR (DXS52) markers. She was considered to be a carrier, and she carried a male foetus by AMXY PCR and chromosome analysis of amniocytes. Foetus did not have mutant haplotype as his uncle, suggesting a normal male status. Our study demonstrates the utility of two new intragenic markers in FVIII gene for carrier detection and prenatal diagnosis of haemophilic families.

Detection of female premutation (PM) carriers of fragile X syndrome may be important in that a PM allele from the mother can expand to a full mutation (FM) when transmitted to the fetus. Although the PM carrier frequency might be different in varying populations, there is a little data on the Korean population. Furthermore, the risks of expansion to FM have not been studied in Korean PM carriers. In this retrospective study, we estimated the female PM carrier frequency and the risks of expansion to FM in Korean diagnostic samples collected for FMR1 gene testing. Of 10,241 pre-conceptional or pregnant women, 13 PM [1 in 788; 95% confidence interval (CI), 1/1,250-1/455] and 75 intermediate allele carriers (1 in 137; 95% CI, 1/172-1/110) were identified. In 26 prenatal diagnoses cases, the PM allele was transmitted to the fetus in 13 pregnancies (50%), and five of these expanded to FM. All of the maternal alleles exceeding 70 repeats expanded to FM. In conclusion, the PM frequency in Korean diagnostic samples was lower than that reported in Western populations, while the risk for FM expansion in alleles exceeding 70 repeats might be higher than expected based upon previous reports.