Carrier detection and prenatal diagnosis in families with haemophilia

Back;ground. Haemophilias are the commonest X-linked disorders affecting ap proximately 1 in 10 000 male births. Detection of carrier women in families with haemophilia and subsequent antenatal diagnosis of confirmed carders a re important services for these patients and their relatives. Over the last 6 years we performed carrier detection and antenatal diagnosis in families with patients of haemophilia A and B, Methods During the last 6 years, 159 families with haemophilia A and B were analysed for carder detection by DNA analysis, using various polymorphic m arkers of factors VIII and IX genes, The polymorphisms used were intron 18 Eel I, intron 19 Hind III, intron 22 Xbal and DXS52/St14 of the factor VIII gene and intron I Ddel, intron 4 TaqI, 3 Hhal and Residue 148 codon Mnll o f the factor IX gene, There were 189 probable carriers (whose carder status was not known) and 99 obligatory carders (confirmed carders by family pedi gree analysis) from 102 families with haemophilia A. Of the 57 families wit h haemophilia B analysed, there were 98 probable and 52 obligatory carders. All the analyses were carried out by polymerase chain reaction, For antena tal diagnosis, prior to polymorphism analysis, the sex of the foetus was de tected by Y chromosome-specific amplification. Results, One hundred and four females were diagnosed as carders and 63 as n on-carders by the intragenic polymorphic markers in families with haemophil ia A, Eighteen women were informative with only the extragenic marker of fa ctor VIII gene. Four women were not informative with any of the markers use d. In families with haemophilia B, 37 women were diagnosed as carriers and 34 as non-carriers by the intragenic markers and 34 were informative only w ith the extragenic markers. Seventeen women were not informative with any o f the markers used. Of the 25 antenatal diagnoses performed (20 haemophilia A, 5 haemophilia B) using the same markers as those used in carder detecti on, 14 were male foetuses and 1 1 female as detected by Y chromosome-specif ic polymerase chain reaction, Eight were affected males and 6 unaffected. A mong the females, 5 were carders and 6 normal. Conclusion. Using the above polymorphic markers of factors VIII and IX gene s, a diagnosis could be made in the majority of families.