Diagnosing and preventing inherited disease: Detection of sickle gene by coelocentesis in early pregnancy: a new approach to prenatal diagnosis of single gene disorders

Coelomic fluid, placental tissue and maternal blood were collected at 7-10 weeks gestation from each of 58 women undergoing elective termination of pregnancy for psychological indications. In all samples, a 364 bp fragment of the human β-globin gene spanning positions -23 to 341 was amplified. The restriction endonuclease Ddel was used to detect the sickle mutation which abolishes its restriction site. β-Globin DNA was successfully amplified from all samples. In 53 cases a normal maternal β-globin genotype was detected. In three out of five cases, where the maternal haemoglobin phenotype was HbAS, heterozygosity for the sickle mutation was demonstrated on analysis of coelomic fluid. In the remaining two cases a normal β-globin genotype was observed. Three further coelomic fluid samples were found to be heterozygous for the sickle mutation. In these instances the maternal haemoglobin phenotype was normal, indicating paternal transmission of the sickle gene. The results of the present study have established that the diagnosis of sickle cell anaemia, and potentially other human single gene disorders, is feasible by coelocentesis.