Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/31455
Title: Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers
Authors: Arashiro, Patricia
Eisenberg, Iris
Kho, Alvin T.
Cerqueira, Antonia M. P.
Canovas, Marta
Silva, Helga Cristina Almeida da [UNIFESP]
Pavanello, Rita C. M.
Verjovski-Almeida, Sergio
Kunkel, Louis M.
Zatz, Mayana
Universidade de São Paulo (USP)
Howard Hughes Med Inst
Harvard Univ
Universidade Federal de São Paulo (UNIFESP)
Keywords: expression profiling
microarray
skeletal muscle
Issue Date: 14-Apr-2009
Publisher: Natl Acad Sciences
Citation: Proceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 106, n. 15, p. 6220-6225, 2009.
Abstract: Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder that has been associated with a contraction of 3.3-kb repeats on chromosome 4q35. FSHD is characterized by a wide clinical inter- and intrafamilial variability, ranging from wheelchair-bound patients to asymptomatic carriers. Our study is unique in comparing the gene expression profiles from related affected, asymptomatic carrier, and control individuals. Our results suggest that the expression of genes on chromosome 4q is altered in affected and asymptomatic individuals. Remarkably, the changes seen in asymptomatic samples are largely in products of genes encoding several chemokines, whereas the changes seen in affected samples are largely in genes governing the synthesis of GPI-linked proteins and histone acetylation. Besides this, the affected patient and related asymptomatic carrier share the 4qA161 haplotype. Thus, these polymorphisms by themselves do not explain the pathogenicity of the contracted allele. Interestingly, our results also suggest that the miRNAs might mediate the regulatory network in FSHD. Together, our results support the previous evidence that FSHD may be caused by transcriptional dysregulation of multiple genes, in cis and in trans, and suggest some factors potentially important for FSHD pathogenesis. the study of the gene expression profiles from asymptomatic carriers and related affected patients is a unique approach to try to enhance our understanding of the missing link between the contraction in D4Z4 repeats and muscle disease, while minimizing the effects of differences resulting from genetic background.
URI: http://repositorio.unifesp.br/handle/11600/31455
ISSN: 0027-8424
Other Identifiers: http://dx.doi.org/10.1073/pnas.0901573106
Appears in Collections:Em verificação - Geral

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