SMALL MUTATION SCREENING IN THE DMD GENE BY WHOLE EXOME SEQUENCING OF AN ARGENTINE DUCHENNE/BECKER MUSCULAR DYSTROPHIES COHORT

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

NEUROMUSCULAR DISORDERS

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2018 vol. 28 p. 986 - 995

0960-8966

AbstractDystrophinopathies are neuromuscular X-linked recessive diseases caused by mutations in the DMD gene. This study aimed to identify DMD gene small mutations by Whole Exome Sequencing (WES), in order to confirm clinical diagnosis, identify candidates for Ataluren treatment and perform carrier status testing. Furthermore, was our goal to characterize the DMD sequence variants and identify co-segregating haplotypes. We analyzed 40 non-related individuals (38 affected boys and 2 at-risk women) with negative MLPA 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 Ataluren candidates and exclude 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 abundance than others. Also, we have detected the existence of 2 co-segregating haplotypes blocks. Finally, this work represents the first DMD gene small mutations screening applying WES in an argentine cohort, contributes with the characterization of our population and collaborates with the DMD small mutation´s knowledge.