GENETIC/MOLECULAR ANALYSIS OF AN ARGENTINE COHORT AFFECTED WITH DUCHENNE/BECKERMUSCULAR DISTROPHIES

LUCE, LEONELA; MAZZANTI, CHIARA; ; CARCIONE, MICAELA; ; SZIJAN, IRENE; ; GILIBERTO, FLORENCIA

Exposici�n; JORNADA DE DIVULGACIÓN DE LAS ACTIVIDADES DEL DEPARTAMENTO DE MICROBIOLOGÍA.INMUNOLOGÍA, BIOTECNOLOGÍA Y GENÉTICA. FACULTAD DE FARMACIA Y BIOQUÍMICA. UNIVERSIDAD DE BUENOS AIRES.; 2018

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GENETIC/MOLECULAR ANALYSIS OF AN ARGENTINE COHORT AFFECTED WITH DUCHENNE/BECKER MUSCULAR DISTROPHIES.Luce, Leonela1,2; Mazzanti, Chiara1,2; Carcione, Micaela1,2; Szijan, Irene1; Giliberto, Florencia1.2.1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Genética. Buenos Aires, Argentina.2CONICET - Universidad de Buenos Aires, Instituto de Inmunología, Genética y Metabolismo (INIGEM). Buenos Aires, Argentina.Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) are X-linked genetic diseases caused by mutations in the DMD gene. DMD is a severe dystrophy that affects 1:3500 born males, whereas BMD is less severe and affects 1:18000. De novo mutations and germline mosaicism are responsible for 1/3 of DMD/BMD cases, while family history (more than 1 affected boy) accounts for the remaining cases. Molecular alterations in DMD gene are gross deletions/duplications in 80% of cases and small mutations in 20%. Hitherto there is no effective treatment for these pathologies, which enhances the importance of performing genetic assessment to the affected families in order to detect mutation carriers and prevent diseased newborns. However, two mutation-specific gene therapies for DMD were recently approved: Exon Skipping of exon 51 and Premature Stop Codon Read-through (Ataluren). Therefore, accurate detection and characterization of the causing mutation is essential to allow genetic counseling, patient follow-up and determine the suitable gene therapy. As there is no ?Gold standard? technique, a diagnostic algorithm must be designed for each case. We implement MLPA, simplex PCR, Whole Exome Sequencing, Sanger Sequencing and STRs segregation analysis. During the last 6 years, we have analyzed approximately 387 samples of affected children and their families, including 14 chorionic villus samples. From the 155 DMD/BMD boys, we have found gross deletion/duplications in 52,3% and small mutations in 21,3%. 13 were candidates for the Exon Skipping therapy, while 17 were suitable for Ataluren. On the other hand, we were able to establish as carrier/affected 38/212 individuals and exclude from being carriers 101/212. The work we have been performing since 1992, allow the characterization of the DMD/BMD argentine population and contribute to the understanding of the genetic/molecular basis of these pathologies.