DYSTROPHIN GENE ANALYSIS AND PRENATAL-DIAGNOSIS OF DUCHENNE MUSCULAR-DYSTROPHY IN RUSSIA

Of 126 families referred for counselling of Duchenne muscular dystroph y (DMD), DNA analysis has been suggested to 119 families with at least one affected child or with an affected close male relative of the wom an at risk of being a DMD carrier. A large proportion (about 80 per ce nt) of the families were represented by sporadic cases (only one affec ted individual). By means of multiplex polymerase chain reactions with different sets of oligoprimers providing amplification of 10-11 diffe rent exons, altogether 49 dystrophin gene deletions were identified (4 1 per cent). Eighteen deletions clustered in the 5' 'hot spot' region of DMD cDNA and 36 in the distal half of the central rod domain around exons 43-53. An unusually high frequency (18 per cent) of deletions i nvolving exons 17-19 was discovered. Large deletions extending through both 'hot spot' regions and thus occupying over 30-40 exons were reco rded in five cases (10 per cent). Seventy-six of 94 families were foun d to be informative by RFLP analysis for intragenic or extragenetic DN A probes. Carrier status was ascertained in 20 and rejected in 32 fema le relatives in 40 DMD families. Eight DMD-affected fetuses were diagn osed prenatally by direct deletion testing or by RFLP analysis. Feasib le interpopulation variations in the dystrophin gene deletion pattern are discussed. The prospects for more effective prenatal diagnosis and carrier detection in high-risk DMD families in Russia are briefly out lined.