DMD carrier detection in a female with mosaic Turner's syndrome.

We are at present trying to identify DMD carriers by gene dosage analyses in those DMD families where the patient exhibits a deletion within one of the DMD-1 cDNA clones.' In the study of one such family using 2 7 probe 8, a deletion of the 1-25, 3-8, 1-6, and 3-7 kb HindIII fragments was seen in a boy with DMD. Visual inspection of the intensity of the 3 8 and 3 7 kb (6 bands diagnosed subjects 1, 3, and 6 as non-carrier females and subjects 2, 4, and 5 as DMD carriers (fig 4 1). However, the pattern in subject 8 was difficult to determine as the bands exhibited an intensity between the normal male and the non-carrier female pattern (fig 1). In spite of the careful measurements of DNA concentration usually carried out when using cDNAs for DMD carrier detection, we studied this family again and obtained the same results. Having requested additional information from the hospital that sent us the samples, it was reported that subject 8 had had previous cytogenetic study of peripheral blood which showed 80% 45,X, 20% 46,XX (mosaic Turner's syndrome). Subsequently, we performed complete haplotyping with intra-and extragenic probes in this family (fig 2). In patient 8, alleles of paternal origin show normal intensity, whereas the faint bands visible only with informative markers correspond to the X chromosome of maternal origin. The results of these studies confirmed the DMD carrier diagnosis done with cDNA probes in subjects 1, 2, 3, 4, 5, and 6. On the autoradiograph obtained after the usual exposure time, the DNA sample Figure I HindIIIfragments detected by cDNA probe 8. Dosage analysis on visual inspection showed reduced intensity of Unitat de Genetica Molecular, Hospital de la Santa Creu i the bands deleted in the male patient and in subjects 2, 4, andS Sant Pau, Unitat de Conseil Reproductiu, Hospital Clinic, and normal band intensity in subjects 1, 3 and 6. Subject 8 shows Barcelona, Spain. an intensity ofthe 3.8 and 3.7 kb bands between normal male for all the polymorphic markers used. However, keeping in mind the existence of the Turner mosaic,