Prenatal Prediction of Autosomal Dominant Diseases by Linkage Studies: Myotonic Dystrophy
Acta geneticae medicae et gemellologiae
Remarkable progress in adapting specific chromosomal and biochemical tests to amniotic fluid samples has allowed intrauterine diagnosis for an increasing number of inherited conditions. However, the lack of any specific tests for autosomal dominant diseases, especially those affecting the nervous system and muscle, has precluded such prenatal evaluation in genetic counseling. Genetic linkage offers a potentially useful alternative approach to such diseases. The gene for a particular disorder
... t be closely linked to a genetic marker which can be analyzed in amniotic fluid or cells obtained in the second trimester of pregnancy. We have recently applied linkage studies to the prediction of myotonic dystrophy (Dm) during pregnancy. Dm is known to be closely linked to the secretor locus (Se), which determines the secretion of ABH blood-group substances into saliva and other body fluids, including the amniotic fluid of the fetus. Only certain families will be suitable for this analysis: the affected parent must have thesecretor-positive phenotype and be heterozygous (Se/se) at the secretor locus; the coupling of the Dm allele to the Se or se allele must be determined; and the spouse must be either secretor-negative or heterozygous secretor-positive. Secretor genotypes can be inferred from secretor phenotypes of close relatives, including the fetus at risk. Unfortunately, these criteria will be satisfied in only 5-10 percent of couples at risk to transmit myotonic dystrophy. In suitable couples, however, linkage analysis can be quite helpful.