Prenatal diagnosis of sickle cell anemia and beta-thalassemia by amniocentesis.
Prenatal diagnosis by amniocentesis alone is possible for about 90% of pregnancies at risk for sickle cell anemia and about 70-75% of pregnancies at risk for beta-thalassemia. It should be stressed that to obtain these percentages, a previous homozygous normal or affected child or, alternatively, the couple's parents are needed to confirm the linkage of variant genes to respective DNA markers (polymorphic restriction sites). Families at risk should be studied prior to or early in pregnancy to determine whether these methods will be applicable to their specific case. If appropriate markers are identified and their linkage to the genes being studied is verified, then prenatal diagnosis by amniocentesis can be done at 16-18 weeks; and for these couples, fetoscopy, with its increased risk of fetal loss, can be avoided. The change of errors in diagnosis due to crossing-over between the mutant gene and the linked marker is small. The probability of such a recombination between the beta-globin gene and the polymorphic G gamma Hind III or the 3' Hpa I site is 1/3,000 and 1/14,000 per generation, respectively (13). A more serious problem is non-paternity because of the errors caused in linkage analysis. Improved methods to enable direct detection of the beta S and/or beta thal mutations would remove both of these potential sources of error.
D000649:Amniocentesis; D000755:Anemia, Sickle Cell / Q000175:diagnosis* / Q000235:genetics; D004262:DNA Restriction Enzymes / Q000235:genetics; D005260:Female; D005332:Fetoscopy; D005796:Genes; D008040:Genetic Linkage; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000175:diagnosis* / Q000235:genetics; D011262:Pregnancy Trimester, Second; D013789:Thalassemia / Q000175:diagnosis*
D004262:DNA Restriction Enzymes