SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy: predicting the severity of Duchenne muscular dystrophy: implications for treatment.

PREDICTING THE SEVERITY OF DUCHENNE MUSCULAR DYSTROPHY: IMPLICATIONS FOR TREATMENT To the Editor: Variability in disease severity in Duchenne muscular dystrophy (DMD) is considered a biological phenomenon, possibly due to genetic or epigenetic mechanisms. It was exciting to read the article by Pegoraro et al.1 describing the discovery of osteopontin as a possible modifier gene. As discussed in the accompanying editorial by Drs. Nelson and Griggs,2 utrophin and myostatin are 2 other proteins modifying disease severity in the mdx mouse. However, human data supporting an important role for utrophin were not mentioned. Kleopas et al.3 demonstrated that utrophin expression in the initial diagnostic muscle biopsies of patients with DMD correlates with time to becoming wheelchair-bound after controlling for steroid treatment and age at biopsy. Transcription of utrophin in muscle fiber remains constant throughout its lifespan in both normal and DMD muscle.4 It would be interesting to know if Pegoraro et al. compared utrophin mRNA transcripts in patients with mild vs severe DMD.