title: Comprehensive oligonucleotide array-comparative genomic hybridization analysis: new insights into the molecular pathology of the DMD gene.
abstract: We report on the effectiveness of a custom-designed oligonucleotide-based comparative genomic hybridization microarray (array-CGH) to interrogate copy number across the entire 2.2-Mb genomic region of the DMD gene and its applicability in diagnosis. The high-resolution array-CGH, we developed, successfully detected a series of 42 previously characterized large rearrangements of various size, localization and type (simple or complex deletions, duplications, triplications) and known intronic CNVs/Indels. Moreover, the technique succeeded in identifying a small duplication of only 191 bp in one patient previously negative for DMD mutation. Accurate intronic breakpoints localization by the technique enabled subsequent junction fragments identification by sequencing in 86% of cases (all deletion cases and 62.5% of duplication cases). Sequence examination of the junctions supports a role of microhomology-mediated processes in the occurrence of DMD large rearrangements. In addition, the precise knowledge of the sequence context at the breakpoints and analysis of the resulting consequences on maturation of pre-mRNA contribute to elucidating the cause of discrepancies in phenotype/genotype correlations in some patients. Thereby, the array-CGH proved to be a highly efficient and reliable diagnostic tool, and the new data it provides will have many potential implications in both, clinics and research.
authors.affiliation: Université Montpellier 1, UFR médecine, Montpellier Cedex 5, France. aliya.ishmukhametova@inserm.fr
authors.forename: Aliya
authors.initials: A
authors.lastname: Ishmukhametova
authors.forename: Philippe
authors.initials: P
authors.lastname: Khau Van Kien
authors.forename: Déborah
authors.initials: D
authors.lastname: Méchin
authors.forename: Delphine
authors.initials: D
authors.lastname: Thorel
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Vincent
authors.forename: François
authors.initials: F
authors.lastname: Rivier
authors.forename: Christine
authors.initials: C
authors.lastname: Coubes
authors.forename: Véronique
authors.initials: V
authors.lastname: Humbertclaude
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tuffery-Giraud
mesh_terms: D002869:Chromosome Aberrations; D056905:Chromosome Breakpoints; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics
chemical_list: C484258:DMD protein, human; D016189:Dystrophin