Background: Mental retardation is a clinical feature of Duchenne dystrophy
(DD) and affects about one-third of patients. No clear association has been
found between DNA mutations, protein expression, and IQ scores, although d
istal deletions in the dystrophin gene have been reported in association wi
th intellectual impairment. A role for the brain distal dystrophin isoform
Dp140 was suggested. Objective: To explore the possible association between
cognitive impairment and DNA macrodeletions in the distal part of the gene
, including Dp140 gene region. Methods: Sixty-six patients with DD received
general intelligence assessment by Wechsler Intelligence Scales measuring
full, verbal, and performance IQ. PCR analysis was performed to detect dele
tions in the dystrophin gene, and the Dp140 regulatory region was analyzed
in a subgroup of 12 patients. Statistical analysis was performed by nonpara
metric Wilcoxon rank signed and rank sum tests. Results: Comparison of neur
opsychological and genetic data revealed an association between distal macr
odeletions and cognitive impairment (p < 0.001). Comparing deletions involv
ing the Dp140 gene region with deletions presumably not altering Dp140 expr
ession resulted in even greater significance. Conclusions: These data sugge
st that in DD, distal dystrophin deletions are associated with intellectual
impairment. This study highlights a possible role for the brain distal iso
form Dp140 in normal cognitive development.