title: Concordant utrophin upregulation in phenotypically discordant DMD/BMD brothers.
abstract: 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.
authors: Human Genome and Stem-Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil. Electronic address: mvainzof@usp.br.
authors: Mariz
authors: M
authors: Vainzof
authors: Human Genome and Stem-Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors: Leticia
authors: L
authors: Feitosa
authors: Human Genome and Stem-Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors: Marta
authors: M
authors: Canovas
authors: Human Genome and Stem-Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors: Danielle
authors: D
authors: Ayub-Guerrieri
authors: Human Genome and Stem-Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors: Rita de Cássia M
authors: Rde C
authors: Pavanello
authors: Human Genome and Stem-Cell Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors: Mayana
authors: M
authors: Zatz
mesh_terms: D018450:Disease Progression; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D010641:Phenotype; D035781:Siblings; D015854:Up-Regulation; D049411:Utrophin / Q000378:metabolism*
chemical_list: D049411:Utrophin
keywords: Duchenne dystrophy; Milder progression; Utrophin