The role of STR-(CA)n segregation analysis in the detection of Duchenne muscular dystrophy carriers

FERREIRO VERÓNICA,; GILIBERTO FLORENCIA, ; SZIJAN IRENE.

Iguassu Falls, Brazil.

Congreso; 10th International Congress of the world muscle society” “Neuromuscular Disorders”; 2005

G.P.3.03 The role of STR-(CA)n segregation analysis in the detection of Duchenne muscular dystrophy carriers. V. Ferreiro, F. Giliberto, I. Szijan Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Genética y Biología Molecular, Buenos Aires, Argentina Duchenne and Becker muscular distrophies (DMD, BMD) are caused by mutations in the dystrophin gene at Xp21.2, they include gross deletions (60%) duplications (10%) and small mutations (30%). Since there is no cure or effective treatment for progressive muscular dystropy, prevention of the disease is important and strongly depends on carrier status information. In order to assess the carrier-risk in female relatives segregation analysis of polymorphism was used to conform the haplotypes of females and patients which identify the mutant dystrophin gene. 52 families were studied with up to 11 STR-(CA)n loci. Leukocyte DNA was amplified by PCR, electrophoresed on polyacrylamide gel and autoradiographed. 75% of female relatives from familial cases were diagnosed as carriers or non-carriers with a 95% likelyhood and 32% of female relatives from sporadic cases could be excluded from the risk. In addition STR studies detected goss deletions in 25% of the families, both in male and female individuals, four of them were “de novo”. STR analyses were also informative without an available DNA sample of an affected male and in two out of 7 symptomatic females. Determination of carrier status was greatly significant for prediction of DMD-risk in prenatal analysis of 5 male-chorionic villi. Other genetic events revealed by STR analysis were: i) 11 recombinations, identified in 6.6% of meiosis in the DMD families. ii)  Germinal mosaicism described in two female-carriers. iii) changes in STR-(CA)n length during transmission from father to daughters, 3 retractions and one elongation, at an estimated rate of 0.004.