SPORADISM INVESTIGATION AND CARRIER DETECTION IN HAEMOPHILIA A BY RFLP ANALYSIS

Restriction fragment lenght polymorphisms (RFLPs)analysis has been employed for carrier detection andfor sporadism study in Haemophilia A. Three RFLPs, one intragenic in FC8 (647/BcII) and two with close linkage to Haemophilia A at DXS52 (Stl4/Taql) and DXS15 (DX13/BgIII), were used.In 20 families 29 carrier status determinations havebeen performed.In order to investigate sporadicity and to estimate the sex ratio of mutation rates directely, 17 families with isolated cases of haemophilia A were studied.In eight out of the 17 families the RFLPsanalysis excluded the carrier status of the maternalgrandmothers.Since by hemostatic studies the eight mothers of the propositi were shown to be haemophilia carriers, the origin of the newly mutated genes was inferred from the RFLP patterns: six haemophilic genes derive from the normal maternal grandfathers and two from the maternal grandmothers.Possible recombinations between FVIII locus and the extragenic RFLPs loci have to be considered; however the intragenic Bell RFLP is informative in five out of the eight families and the DXl3 and Stl4 patterns are concordant.The data indicate a higher mutation rate in males than in females gametes as previously suggested, althought not unanimously, by segregation analysis and coagulation studies. The RFLP analysis in a large number of families with isolated cases of haemophilia isnecessary to define the precise ratio of sex mutation rate for this disease.Work supported by P.F. Ing. Gen. Basi Mol. Mai. Ered. Contratto CNR N 8400877.