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Prenatal diagnosis and carrier determination in haemophilia B using three gene-specific polymorphic DNA markers
18
THROMBOSIS
RESEARCH
Suppl . VI,
1986
34
PmALDIAGJ%IS at-idCARRIERDEIERMINATIONin~PHILIABUSINGTHREE CZNE-SPECIFICPOLYIQRPHICDNA MARKERS. F. Giannelli, A. Morris, C.Thurston, R. Warren, R.S. Mibashan. Prince Philip ResearchLaboratories,Guy's Hospital,London SEI, and Depts. of Obstetricsand Haematology,King's College Hospital, Imdon SE5, U.K. Studieshave been perfomsd in 53 femalemembers of 22 haermphiliaB families using 3 factor IX specificDNApolyrmrphisms,Taq I, Xmn I andHinf I. The aim was to providegenetic counsellingby identifyingcarrier status and determiningfetalgenotypewhen indicated. Thirty-tw0wme.nwere either obligate carriers.ormothers of a single affectedindividual,and 23/32 ware heterozygousfor at least one of the markers - a necessaryconditionfor diagnosingdescendants'status by DNA polymorphisms. This result is in keepingwith a theoreticalexpectationof 68% (Winshipet al, NAR, 12:8861, 1984). HaermphiliaB genotypewas also assessedin 21 other wmen who were putativecarriersbecause they belongedto a haemophilicfamily (14)or had a solitaryaffectedrelative (7). Six out of 14 could be confirxedas carriers and amther 6 positivelyexcluded;so far carrier status could only be excluded. in l/7 of the sporadicgroup - but success in this categorywill vaxywithfamilystructure. Early prenataldiagnosisusing these three gene-specificDNA markers was carriedout in one nom1 male, one carrier female and two as yet undeliveredfemale fetuses. 35 LA.V/HTLV III ANTIBODIES IN SWEDISH HAEMOPHILIACS; IN RELATION TO TYPE AND DOSAGE OF FACTOR CONCENTRATE. E. Berntorp, G. Jarevi, A. Vedback and I.M. Nilsson. Department of Coagulation Disorders, Lund University, Malmij General Hospital, Malmo, Sweden. Three groups of haemophilia A patients were formed according to LAV/HTLV III antibody status and type of factor concentrate used in treatment. Group 1 comprised 36 seropositive patients, groups 2 and 3 44 and 25 seronegative patients, respectively. Groups 1 and 2 were treated with factor concentrates of American plasma origin and also in most cases with concentrates of Swedish origin. Group 3 received Swedish concentrates only. Seroconversion in group 1 was established by retrospective LAV/HTLV III antibody testing of sera stored frozen for several years. Most patients had seroconverted in 1980-82 (n=22), and in no patient could seroconversion be found after the introduction of heat-treated American factor concentrates in Jan 1983. The groups had received comparable amounts of factor concentrate, about 2000 U per kg and year. The ratio between Swedish and American concentrates was 0.84 and 3.33 in groups 1 and 2, respectively. Two patients in group 1 had each received only one batch of American factor concentrate (4000 and 15,000 U). Without causing seroconversion, 69,000 U of the same batch had been given to one group 2 patient who also had a normal T4/T8 ratio. We conclude that LAV/HTLV III has been transmitted to Swedish haemophiliacs by American factor concentrates before 1983 when heat treatment was introduced, though there is great diversity in susceptibility to LAV/HTLV III.
THROMBOSIS
RESEARCH
Suppl . VI,
1986
34
PmALDIAGJ%IS at-idCARRIERDEIERMINATIONin~PHILIABUSINGTHREE CZNE-SPECIFICPOLYIQRPHICDNA MARKERS. F. Giannelli, A. Morris, C.Thurston, R. Warren, R.S. Mibashan. Prince Philip ResearchLaboratories,Guy's Hospital,London SEI, and Depts. of Obstetricsand Haematology,King's College Hospital, Imdon SE5, U.K. Studieshave been perfomsd in 53 femalemembers of 22 haermphiliaB families using 3 factor IX specificDNApolyrmrphisms,Taq I, Xmn I andHinf I. The aim was to providegenetic counsellingby identifyingcarrier status and determiningfetalgenotypewhen indicated. Thirty-tw0wme.nwere either obligate carriers.ormothers of a single affectedindividual,and 23/32 ware heterozygousfor at least one of the markers - a necessaryconditionfor diagnosingdescendants'status by DNA polymorphisms. This result is in keepingwith a theoreticalexpectationof 68% (Winshipet al, NAR, 12:8861, 1984). HaermphiliaB genotypewas also assessedin 21 other wmen who were putativecarriersbecause they belongedto a haemophilicfamily (14)or had a solitaryaffectedrelative (7). Six out of 14 could be confirxedas carriers and amther 6 positivelyexcluded;so far carrier status could only be excluded. in l/7 of the sporadicgroup - but success in this categorywill vaxywithfamilystructure. Early prenataldiagnosisusing these three gene-specificDNA markers was carriedout in one nom1 male, one carrier female and two as yet undeliveredfemale fetuses. 35 LA.V/HTLV III ANTIBODIES IN SWEDISH HAEMOPHILIACS; IN RELATION TO TYPE AND DOSAGE OF FACTOR CONCENTRATE. E. Berntorp, G. Jarevi, A. Vedback and I.M. Nilsson. Department of Coagulation Disorders, Lund University, Malmij General Hospital, Malmo, Sweden. Three groups of haemophilia A patients were formed according to LAV/HTLV III antibody status and type of factor concentrate used in treatment. Group 1 comprised 36 seropositive patients, groups 2 and 3 44 and 25 seronegative patients, respectively. Groups 1 and 2 were treated with factor concentrates of American plasma origin and also in most cases with concentrates of Swedish origin. Group 3 received Swedish concentrates only. Seroconversion in group 1 was established by retrospective LAV/HTLV III antibody testing of sera stored frozen for several years. Most patients had seroconverted in 1980-82 (n=22), and in no patient could seroconversion be found after the introduction of heat-treated American factor concentrates in Jan 1983. The groups had received comparable amounts of factor concentrate, about 2000 U per kg and year. The ratio between Swedish and American concentrates was 0.84 and 3.33 in groups 1 and 2, respectively. Two patients in group 1 had each received only one batch of American factor concentrate (4000 and 15,000 U). Without causing seroconversion, 69,000 U of the same batch had been given to one group 2 patient who also had a normal T4/T8 ratio. We conclude that LAV/HTLV III has been transmitted to Swedish haemophiliacs by American factor concentrates before 1983 when heat treatment was introduced, though there is great diversity in susceptibility to LAV/HTLV III.