OBJECTIVETo establish the linkage methods of X ba I polymorphisms specific for FVIII gene intron 22, and to find a rapid and simple system for haemophilia A (HA) carrier detection and prenatal diagnosis.

METHODSA long PCR to amplify FVIII gene intron 22 followed by X ba I digestion was used to assay the gene rate and heterozygosity rate of 206 unrelated people. Detection of intron 22 inversion by long distance PCR (LD-PCR) and XbaI, BclI, Hind III, DXS52, STR polymorphism within intron 13 and 22 by hereditary linkage analysis were assays in 20 HA pedigrees.

RESULTSThe gene rate and polymorphism information contents of 206 people were 0.5475 and 0.4955 respectively, 7 of 20 HA families were diagnosed as intron 22 inversion, 6 of 13 non-inversion HA families were diagnosed by X ba I linkage analysis, 8 of 13 non-inversion HA families were diagnosed by two or more linkage analysis.

CONCLUSIONSThe improved X ba I linkage analysis is a specific and useful molecular diagnosis marker. LD-PCR and five-linkage analysis can be used in prenatal HA gene diagnosis.