INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SMALL MUTATION DETECTION IN THE DMD GENE BY WHOLE EXOME SEQUENCING OF ARGENTINE DYSTROPHINOPATHY CHILDREN
Autor/es:
CARCIONE, MICAELA; DUBROVSKY, ALBERTO; MAZZANTI, CHIARA}; GILIBERTO FLORENCIA; LEONELA, LUCE; MESA, LILIA
Lugar:
Mendoza
Reunión:
Congreso; World Muscle Society Congress; 2018
Institución organizadora:
World Muscle Society
Resumen:
Dystrophinopathies are neuromuscular X-linked recessive diseases caused by mutations in the DMD gene. The present study aimed to identify DMDgene small mutations by Whole Exome Sequencing (WES), in order to confirm clinical diagnosis, identify candidates for Premature Termination Codon(PTC) Read-through treatments and perform carrier status testing. Furthermore, was our goal to characterize the identified DMD sequence variants anddetermine the existance of co-segregating haplotypes. We analyzed 40 non-related individuals (38 affected boys and 2 at-risk women) with negativeMLPA results. The WES and the implemented pathogenic variant selection algorithm probed to be efficient, showing a detection rate of ~84% (32/38).We have found 15 nonsense mutations, 9 deletions/duplications and 8 splice site mutations. We could identify 15 PTCs read-through candidates andexclude 2 at-risk women. The characterization of the occurrence and diversity of DMD sequence variants from our cohort and from LOVD database,revealed no hot spots but showed exons/introns unlikely to carry small molecular alterations and exons presenting a greater mutagenic abundancethan others do. In addition, we have detected two co-segregating haplotypes blocks, which might have an european origin. Finally, this work representsthe first DMD gene small mutations screening applying WES in an argentine cohort, contributes with the characterization of our population andcollaborates with the DMD small mutation´s background.