Hypoalphalipoproteinaemia and polymorphisms associated with reduced expression of the apolipoprotein A-I gene and resolution of disputed paternity in a large English family.

A Pst-I RFLP polymorphism adjacent to the 3' end of the apolipoprotein A-I gene is reported to associate with hypoalphalipoproteinaemia with dominant inheritance in families identified through accelerated coronary heart disease. This association was not apparent in a large English family identified through voluntary health screening, and with no evident premature coronary disease. Any association could, however, be masked by sex, or by further undetermined variation affecting Pst-I restriction sites. Analysis of this and other polymorphisms present also led to resolution both of disputed paternity and of a long-standing family feud.

Haematological aspects of antenatal diagnosis for thalassaemia in Britain.

The results are described of 200 antenatal diagnostic tests for haemoglobinopathies performed on samples of fetal blood obtained during the second trimester of pregnancy. Haemoglobin A synthesis in the fetus was measured by incorporation of tritiated leucine in vitro and separation of the globin chains on CM23 columns. The range of HbA synthesis detected was 3.5-8.0% in normal fetuses, 2.0-5.0% in fetuses with thalassaemia trait, and less than 1.6% in fetuses with thalassaemia major. There were eight cases in which other haemoglobinopathies were diagnosed. 29% of the pregnancies were terminated because thalassaemia major was diagnosed, and 9.5% of the remaining healthy fetuses were lost for obstetric reasons. Follow up has been possible for 96% of the 124 surviving babies and three misdiagnoses have come to light; one false positive (0.5%) and two false negatives (1%). These figures represent a first effort at antenatal diagnosis for haemoglobinopathies and it is likely that they will improve with the passage of time.

Antenatal search for fetal beta-thalassaemia in a twin pregnancy.

The antenatal search for fetal beta-thalassaemia in a twin pregnancy is described. Thalassaemia major was correctly excluded in both fetuses, and some of the problems of identifying patients at risk are outlined as well as those of obtaining fetal blood in the second trimester of pregnancy.