Case reportConcordant utrophin upregulation in phenotypically discordant DMD/BMD brothers

- A study of utrophin in rare phenotypically discordant DMD brothers was done.
- Utrophin amount was increased 3.4 and 3.3 fold in the two brothers on blots.
- Utrophin was equally upregulated in severe and mild DMD/BMD half-brothers.
- Milder phenotype in an exceptional DMD patient is not caused by utrophin over expression.

Utrophin expression was investigated in two phenotypically discordant Duchenne muscular dystrophy half-brothers. The youngest was wheelchair-bound at age 9, while his mildly affected older brother was able to walk without difficulties at age 15. DNA analysis revealed an out-of-frame exon 2 duplication in the DMD gene, associated with muscle dystrophin protein deficiency. Utrophin localization and quantity was analyzed and compared in both sibs to verify whether this could explain the milder phenotype of the older brother. Immunofluorescence analysis showed a clear sarcolemmal labeling for utrophin in both of them, which was present in regenerating as well as in mature fibers. On western blot analysis, utrophin amount was increased 3.4 and 3.3 fold respectively, as compared to normal controls, while it was increased 1.7 to 4.0 fold in a group of DMD patients within the typical range of clinical progression. These data are in accordance with our previous observations suggesting no correlation between phenotype severity and utrophin up-regulation or sarcolemmal localization in dystrophinopathies. Finding the protective mechanisms in patients with milder course is of utmost interest to direct therapeutic targets.