MLPA analysis of an Argentine cohort of patients with dystrophinopathy: Association of intron breakpoints hot spots with STR abundance in DMD gene

LUCE, LEONELA; PARMA, DIANA; FERRER, MARCELA; GILIBERTO, FLORENCIA; DALAMON, VIVIANA; SZIJAN, IRENE

JOURNAL OF THE NEUROLOGICAL SCIENCES

ELSEVIER SCIENCE BV

Lugar: Amsterdam ; Año: 2016 vol. 365 p. 22 - 30

0022-510X

Dystrophinopathies are X-linked recessive diseases caused by mutations in the DMD gene. Our objective was toidentify mutations in this gene by Multiplex Ligation Probe Amplification (MLPA), to confirm the clinical diagnosisand determine the carrier status of at-risk relatives. Also, we aimed to characterize the Dystrophinopathies argentinepopulation and the DMD gene. We analyzed a cohort of 121 individuals (70 affected boys, 11symptomatic women, 37 at-riskwomen and 3 male villus samples). TheMLPA technique identified 56mutations(45 deletions, 9 duplications and 2 point mutations). These results allowed confirming the clinical diagnosis in63% (51/81) of patients and symptomatic females. We established the carrier status of 54% (20/37) of femalesat-risk and 3 male villus samples.We could establish an association between the most frequent deletion intronbreakpoints and the abundance of dinucleotide microsatellites loci, despite the underlying mutational molecularmechanismremains to be elucidated. TheMLPA demonstrate, again, to be the appropriate first mutation screeningmethodology for molecular diagnosis of Dystrophinopathies. The reported results permitted to characterizethe Dystrophinopathies argentine population and lead to better understanding of the genetic and molecularbasis of rearrangements in the DMD gene, useful information for the gene therapies being developed