Dystrophin deletions and cognitive impairment Dystrophin deletions and cognitive impairment in Duchenne/Becker muscular dystrophy in Duchenne/Becker muscular dystrophy

GILIBERTO FLORENCIA, FERREIRO VERO´NICA, DALAMON VIVIANA AND SZIJAN IRENE

Neurological Research

Lugar: Detroit, United States; Año: 2004 vol. 26 p. 83 - 87

Analyses of deletions in the dystrophin gene and of cognitive status were performed on patients with Duchenne  (DMD) or Becker  (BMD) muscular  dystrophy  in order  to Žnd a correlation between both features. Molecular study by multiplex and simplex PCR of dystrophin exons led to the identiŽcation of 51 deletions in 126 unrelated patients. Most of them were frameshift, in full agreement with severe clinical symptoms, three patients with a BMD-like phenotype had in-frame mutations. Deletions were localized with reference to the different dystrophin isoform sequences and were clustered in two main areas, 5’ and central ‡ 3’ end of the gene.  Cognitive  abilities  were tested in 47 out of 51 patients  with identiŽed mutations, 23 of them being mentally impaired. Comparison of molecular and neuropsychological features showed that  deletions  localized  in central  and 30  parts of the gene (18 out of 23) are preferentiallyassociated with mental impairment. Fourteen of them were found in the regulatory and coding sequences for the three CNS speciŽc carboxy terminal isoforms. Therefore, though mutations with variable locations may lead to cognitive impairment, our results show that deletions in the distal portion of the gene are basically related to mental retardation.