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DNA probe analysis in the detection of carriers and in the prenatal diagnosis of duchenne muscular dystrophy

Daisy N. Falcão-Conceição^I; E. Bakker^II

^IDepartamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Caixa Postal 68011, Ilha do Fundão, 21941 Rio de Janeiro, RJ, Brasil. Send correspondence to D.N.F.-C.
^IIDepartment of Human Genetics, Sylvius Laboratories, State University of Leiden, Leiden, The Netherlands

ABSTRACT

Prenatal diagnosis at the tenth week of gestation in a male fetus from a proven carrier of the DMD gene will be faster if the restriction fragments length polymorphism (RFLP) markers for which the mother is informative are already known. We investigated a Brazilian DMD family with proven carriers in three generations. Two sisters of the proband, 19 and 8 years old, were shown to be carriers on the basis of repeatedly elevated creatine-kinase levels in relation to age-matched controls. All available members of the three-generation family (maternal grandmother and grandfather, mother, maternal uncle, father, proband and his two sisters) were studied.We used the first stage of the diagnostic procedure proposed by the Leiden group, which consists of digestion of DNA from family members with five enzymes and hybridization of the fragments with seven probes. There was enough information to discriminate the potential DMD chromosome in the patient's mother from that originating from the maternal grandfather, i.e., phase is known in the mother. It was possible to confirm at the 99% confidence level that the two sisters of the patient have inherited the DMD chromosome. Both girls are informative for the two closest flanking DMD locus markers C7 and 754, the information being sufficient to make a prenatal diagnosis in a future male fetus with 99% reliability.No deletions were found in the patient in relation to the pERT87 or XJ1.1 probes. Detected crossings do not interfere with our conclusions with respect to the DMD carrier status of the two sisters of the patient.No deletions were found in the patient in relation to the pERT87 or XJ1.1 probes. Detected crossings do not interfere with our conclusions with respect to the DMD carrier status of the two sisters of the patient.

Keywords: DNA; carriers; prenatal; diagnosis; duchenne muscular dystrophy.

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