Hordozóságszűrés Duchenne-/Becker- izomdystrophiával érintett családokban [Carrier detection in families affected by Duchenne/Becker muscular dystrophy]

Abstract

Duchenne/Becker muscular dystrophy is a severe, recessive, X-linked neuromuscular disease with an incidence of 1/3500 (Duchenne type) and 1/30,000 (Becker type) in newborn boys. The gene responsible for the Duchenne/Becker muscular dystrophy phenotype is located at Xp21 and its 427 kD) protein product is called dystrophin. Deletions, point mutations and rarely duplications can occur almost anywhere in the DMD gene, which makes the molecular diagnosis difficult. Multiple polimerase chain reactions detect 95% of deletions in affected males [2, 4], but are not suitable for carrier detection in female relatives. Southern-blot analysis with six different cDNA probes covers the whole 14 kb dystrophin transcript and allows the detection of female carriers by comparing the intensity of the signals corresponding to the different exons. This method is time consuming compared to the newly introduced multiple ligation-dependent probe amplification method. Multiple ligation-dependent probe amplification is a method suitable for relative quantification of several DNA sequences in one reaction. The authors report results on 93 cases where the carrier status was analysed simultaneously by cDNA hybridisation and multiple ligation-dependent probe amplification technique. In 42 cases the carrier state was confirmed and in this carrier population the authors additionally detected two cases with duplication, two cases with one copy of the whole dystrophin gene and three manifest carrier females. On the basis of these results the MLPA technique, which has been newly introduced in Hungary, proved to be a sensitive and quick method for the detection of carrier state in the DMD/BMD disease. Moreover, the exact deletion or duplication border can be detected and as a result, prediction on the phenotype can be given. This will provide the right therapeutic intervention for the affected patients in the future.