info:eu-repo/semantics/article
Small mutation screening in the DMD gene by whole exome sequencing of an Argentine Duchenne/Becker muscular dystrophies cohort
Date
2018-12Registration in:
Luce, Leonela Natalia; Carcione, María Micaela; Mazzanti, Chiara; Ferrer, Marcela Maria; Szijan, Irene; et al.; Small mutation screening in the DMD gene by whole exome sequencing of an Argentine Duchenne/Becker muscular dystrophies cohort; Pergamon-Elsevier Science Ltd; Neuromuscular Disorders; 28; 12; 12-2018; 986-995
0960-8966
CONICET Digital
CONICET
Author
Luce, Leonela Natalia
Carcione, María Micaela
Mazzanti, Chiara
Ferrer, Marcela Maria
Szijan, Irene
Giliberto, Florencia
Abstract
Dystrophinopathies 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 ancestral haplotypes. We analyzed 40 non-related individuals (38 affected boys with dystrophinopathy presumptive clinical diagnosis and 2 at-risk women) with negative MLPA results. Pathogenic DMD variants were found in 32 boys. Surprisingly, in another 4 patients with absence/deficiency of dystrophin in muscle biopsy, pathogenic variants were found in Limb-girdle muscular dystrophy genes. Therefore, the WES detection rate resulted ∼94% (36/38). 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 hotspots 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.