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Prenatal exclusion of haemophilia a and carrier testing by direct detection of a disease lesion
Author(s) -
Schwartz Marianne,
Cooper David N.,
Millart David S.,
Kakkar Vijay V.,
Scheibel Elma
Publication year - 1992
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.1970121103
Subject(s) - proband , prenatal diagnosis , haemophilia , haemophilia a , coagulopathy , chorionic villus sampling , lesion , medicine , chorionic villi , haemophilia b , mutation , pregnancy , genetics , pathology , fetus , immunology , gene , biology , pediatrics
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.