Prenatal exclusion of haemophilia a and carrier testing by direct detection of a disease lesion |
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Authors: | Marianne Schwartz PhD David N Cooper David S Millart Vijay V Kakkar Elma Scheibel |
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Institution: | 1. Charter Molecular Genetics Laboratory, Thrombosis Research Institute, Manresa Road, London SW3 6LR, U.K.;2. Department of Pediatrics. University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark |
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Abstract: | A novel mutation was detected in the Factor VIII gene of a sporadic case of severe haemophilia A. The lesion, a CGA → TGA transition, converts Arg 795 to Term and adequately accounts for the severe phenotype observed. PCR/direct sequencing was used to confirm the carrier status in the mother. Exclusion of haemophilia A in an at-risk pregnancy was then achieved by demonstration of the absence of this lesion in fetal DNA from a chorionic villus sample. The mutation was also detectable by chemical cleavage of mismatch (CCM), which both confirmed the prenatal diagnosis and established the carrier status of the proband's sister. This example therefore serves to illustrate the potential of direct gene analysis in sporadic cases of haemophilia A and/or in families uninformative for known RFLPs. |
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Keywords: | Factor VIII Point mutation Chemical mismatch cleavage |
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