G.P.126: MRI detects Dp140 dystrophin isoform dependent brain changes in boys with DMD

Abstract

A genotype-phenotype correlation has been suggested for cognitive and behavioral problems associated with Duchenne muscular dystrophy (DMD). We have previously reported changes in cerebral grey matter volume and white matter microstructure in boys with DMD using quantitative MRI. In this post hoc study we used mutation information derived from extensive DNA sequencing to predict the expression of dystrophin isoform Dp140 in our group in order to assess the influence of this isoform on brain anatomy in DMD. The results of anatomical (T1w), and microstructural (DTI) scans, as well as a short neuropsychological examination (NPE), were compared between two DMD subgroups of 12 boys with DMD (age 8–18years old) and age-matched control boys. DMD boys were classified according to predicted Dp140 isoform expression (DMD_Dp140+ and DMD_Dp140−). We show that group DMD_Dp140− differed significantly from controls in terms of both anatomy and microstructure, with reduced grey matter volume and affected white matter microstructure. Group DMD_Dp140+ anatomy and microstructure did not differ significantly from either DMD_Dp140− or controls, but values consistently fell in between these groups. NPE results also show significant differences in information processing between DMD_Dp140− and controls, with DMD_Dp140+ scoring in between control and DMD_Dp140−, but not differing significantly from either. Given that Dp140 is predominantly expressed during fetal development our results suggest an important role for Dp140 in (early) brain development. This further substantiates the importance of looking at the different isoforms in DMD, since not only function is affected, but anatomy and microstructure as well.