[Carrier diagnosis and prenatal prognosis using DNA analysis in X-chromosome-linked Duchenne and Becker muscular...

Haplotypes for 7 flanking and 16 "intragenic" X-linked DNA polymorphisms were determined in 204 members of 31 families with Duchenne (DMD) and 27 members of 4 families with Becker type muscular dystrophy (BMD) and combined with CK and pedigree data to estimate carrier and fetal risks. All of the 27 younger female relatives of the familial cases (8 DMD, 2 BMD) could either be identified (11) or ruled out (16) as carriers with 95% or higher probability. Out of 49 possible carriers in the 23 DMD and 2 BMD families with isolated cases, 19 were classified as carriers and 18 as homozygote-normal females. In 3 families the mutation could be traced indirectly to a defined ancestor (mother, grand-parent), and in 5 families a molecular deletion was found. In all identified carriers and in medium risk females an informative DNA-constellation for prenatal predictions was present for at least one "intragenic" or two flanking markers. Prenatal DNA-investigations were carried out during pregnancy in 9 possible DMD carriers. There was one termination due to an XYY karyotype. Of the remaining 8 cases, the carrier state could be ruled out in 4 mothers, the fetal sex was female in another 3, and one male fetus was predicted normal. All babies (3 boys, 5 girls) are healthy. The practical significance of these findings with regard to the prevention of DMD/BMD and the present diagnostic strategies are discussed.