BACKGROUND: A significant component of the variation in cognitive disability 
that is observed in Duchenne muscular dystrophy (DMD) is known to be under 
genetic regulation. In this study we report correlations between standardised 
measures of intelligence and mutational class, mutation size, mutation location 
and the involvement of dystrophin isoforms.
METHODS AND RESULTS: Sixty two male subjects were recruited as part of a study 
of the cognitive spectrum in boys with DMD conducted at the Sydney Children's 
Hospital (SCH). All 62 children received neuropsychological testing from a 
single clinical psychologist and had a defined dystrophin gene (DMD) mutation; 
including DMD gene deletions, duplications and DNA point mutations. Full Scale 
Intelligence Quotients (FSIQ) in unrelated subjects with the same mutation were 
found to be highly correlated (r = 0.83, p = 0.0008), in contrast to results in 
previous publications. In 58 cases (94%) it was possible to definitively assign 
a mutation as affecting one or more dystrophin isoforms. A strong association 
between the risk of cognitive disability and the involvement of groups of DMD 
isoforms was found. In particular, improvements in the correlation of FSIQ with 
mutation location were identified when a new classification system for mutations 
affecting the Dp140 isoform was implemented.
SIGNIFICANCE: These data represent one of the largest studies of FSIQ and 
mutational data in DMD patients and is among the first to report on a DMD cohort 
which has had both comprehensive mutational analysis and FSIQ testing through a 
single referral centre. The correlation between FSIQ results with the location 
of the dystrophin gene mutation suggests that the risk of cognitive deficit is a 
result of the cumulative loss of central nervous system (CNS) expressed 
dystrophin isoforms, and that correct classification of isoform involvement 
results in improved estimates of risk.