title: MLPA analysis of an Argentine cohort of patients with dystrophinopathy: Association of intron breakpoints hot spots with STR abundance in DMD gene.
abstract: Dystrophinopathies are X-linked recessive diseases caused by mutations in the DMD gene. Our objective was to identify mutations in this gene by Multiplex Ligation Probe Amplification (MLPA), to confirm the clinical diagnosis and determine the carrier status of at-risk relatives. Also, we aimed to characterize the Dystrophinopathies argentine population and the DMD gene. We analyzed a cohort of 121 individuals (70 affected boys, 11 symptomatic women, 37 at-risk women and 3 male villus samples). The MLPA technique identified 56 mutations (45 deletions, 9 duplications and 2 point mutations). These results allowed confirming the clinical diagnosis in 63% (51/81) of patients and symptomatic females. We established the carrier status of 54% (20/37) of females at-risk and 3 male villus samples. We could establish an association between the most frequent deletion intron breakpoints and the abundance of dinucleotide microsatellites loci, despite the underlying mutational molecular mechanism remains to be elucidated. The MLPA demonstrate, again, to be the appropriate first mutation screening methodology for molecular diagnosis of Dystrophinopathies. The reported results permitted to characterize the Dystrophinopathies argentine population and lead to better understanding of the genetic and molecular basis of rearrangements in the DMD gene, useful information for the gene therapies being developed.
authors.affiliation: Laboratory of Dystrophinopathies, Department of Genetics, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina. Electronic address: leonelaluce@gmail.com.
authors.forename: Leonela N
authors.initials: LN
authors.lastname: Luce
authors.affiliation: INGEBI CONICET, Buenos Aires, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Dalamon
authors.affiliation: Molecular Neurobiology Laboratory, Neurosurgery Division, Hospital de Clínicas "José de San Martín", University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Ferrer
authors.affiliation: Laboratory of Dystrophinopathies, Department of Genetics, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Diana
authors.initials: D
authors.lastname: Parma
authors.affiliation: Laboratory of Dystrophinopathies, Department of Genetics, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Irene
authors.initials: I
authors.lastname: Szijan
authors.affiliation: Laboratory of Dystrophinopathies, Department of Genetics, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Giliberto
mesh_terms: D001118:Argentina; D015331:Cohort Studies; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D018895:Microsatellite Repeats; D060885:Multiplex Polymerase Chain Reaction; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation
chemical_list: C484258:DMD protein, human; D016189:Dystrophin
keywords: Carrier detection; Duchenne Muscular Dystrophy; Dystrophinopathies; Gene characterization; MLPA analysis; Molecular diagnosis