Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/67260
Título: | Biallelic variants in the transcription factor PAX7 are a new genetic cause of myopathy |
Autor(es): | Feichtinger, René G. Mucha, Bettina E. Hengel, Holger Orfi, Zakaria Makowski, Christine Dort, Junio D'Anjou, Guy Nguyen, Thi Tuyet Mai Buchert, Rebecca Juenger, Hendrik Freisinger, Peter Baumeister, Sarah Schoser, Benedikt Ahting, Uwe Keimer, Reinhard Nguyen, Cam-Tu Emilie Fabre, Paul Gauthier, Julie Miguet, Marguerite Lopes, Fátima AlHakeem, Afnan AlHashem, Amal Tabarki, Brahim Kandaswamy, Krishna Kumar Bauer, Peter Steinbacher, Peter Prokisch, Holger Sturm, Marc Strom, Tim M. Ellezam, Benjamin Mayr, Johannes A. Schöls, Ludger Michaud, Jacques L. Campeau, Philippe M. Haack, Tobias B. Dumont, Nicolas A. |
Palavras-chave: | Adolescent Alleles Child Child, Preschool Female Humans Male Muscle Development Muscle, Skeletal Muscular Diseases Myoblasts PAX7 Transcription Factor Pedigree Regeneration Satellite Cells, Skeletal Muscle Transcription Factors Whole Exome Sequencing Myopathy Muscle stem cell Myoblasts skeletal muscle PAX7 |
Data: | 2019 |
Editora: | Springer Nature |
Revista: | Genetics in Medicine |
Citação: | Feichtinger, R.G., Mucha, B.E., Hengel, H. et al. Biallelic variants in the transcription factor PAX7 are a new genetic cause of myopathy. Genet Med 21, 2521–2531 (2019) |
Resumo(s): | Skeletal muscle growth and regeneration rely on muscle stem cells, called satellite cells. Specific transcription factors, particularly PAX7, are key regulators of the function of these cells. Knockout of this factor in mice leads to poor postnatal survival; however, the consequences of a lack of PAX7 in humans have not been established. Purpose Skeletal muscle growth and regeneration rely on muscle stem cells, called satellite cells. Specific transcription factors, particularly PAX7, are key regulators of the function of these cells. Knockout of this factor in mice leads to poor postnatal survival; however, the consequences of a lack of PAX7 in humans have not been established. Methods Here, we study five individuals with myopathy of variable severity from four unrelated consanguineous couples. Exome sequencing identified pathogenic variants in the PAX7 gene. Clinical examination, laboratory tests, and muscle biopsies were performed to characterize the disease. Results The disease was characterized by hypotonia, ptosis, muscular atrophy, scoliosis, and mildly dysmorphic facial features. The disease spectrum ranged from mild to severe and appears to be progressive. Muscle biopsies showed the presence of atrophic fibers and fibroadipose tissue replacement, with the absence of myofiber necrosis. A lack of PAX7 expression was associated with satellite cell pool exhaustion; however, the presence of residual myoblasts together with regenerating myofibers suggest that a population of PAX7-independent myogenic cells partially contributes to muscle regeneration. Conclusion These findings show that biallelic variants in the master transcription factor PAX7 cause a new type of myopathy that specifically affects satellite cell survival. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/67260 |
DOI: | 10.1038/s41436-019-0532-z |
ISSN: | 1098-3600 |
e-ISSN: | 1530-0366 |
Versão da editora: | https://www.nature.com/articles/s41436-019-0532-z |
Arbitragem científica: | yes |
Acesso: | Acesso restrito autor |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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feichtinger2019.pdf Acesso restrito! | 2,77 MB | Adobe PDF | Ver/Abrir |