Mutation Location and Cognitive Impairment in Duchenne Muscular Dystrophy

Background: Cognitive impairment is commonly seen in patients with Duchenne muscular dystrophy (DMD). Few studies have shown a correlation between loss of different isoforms of the DMD gene and cognitive impairment.

Objective: The objective of the study was to determine whether correlation exists in the location of mutation in DMD gene or loss of different isoforms and cognitive impairment in children with DMD in the Indian population.

Materials and methods: Ten children were evaluated. Gene mutation analysis was done by multiplex ligation-dependent probe amplification method. The isoforms affected were inferred from mutation location in each of these patients. Binet Kamat Intelligence Test (BKT) and Bender Gestalt test (BGT) were administered.

Results: All male patients were aged between 4 and 9 years. Genetic analysis showed deletion in all patients, with seven having deletion in "hotspot" regions (exon 43-52). Psychometric analysis by BGT and BKT showed mean score of 8.6 and mean IQ score of 85.5, respectively. Comparison between patients with hotspot mutations and mutations in other regions, for mean IQ score and BGT score, was statistically significant (P = 0.132 and P = 0.005, respectively). The difference in the IQ score between patients with isolated Dp427 loss (n = 3) and cumulative Dp427/Dp260/Dp140utr loss (n = 6) was statistically significant (P = 0.011). Visuomotor functioning was more impaired in patients with isolated Dp427 loss.

Conclusion: The role of cumulative loss of isoforms along with importance of loss of Dp140pc isoform was seen in our study. One patient with loss of Dp140utr isoform had intellectual impairment which is not commonly seen. Visuomotor functioning is more affected in more upstream mutations as shown in our study.