Utilize este identificador para referenciar este registo: https://hdl.handle.net/1822/67260

TítuloBiallelic 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-chaveAdolescent
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
Data2019
EditoraSpringer Nature
RevistaGenetics in Medicine
CitaçãoFeichtinger, 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.
TipoArtigo
URIhttps://hdl.handle.net/1822/67260
DOI10.1038/s41436-019-0532-z
ISSN1098-3600
e-ISSN1530-0366
Versão da editorahttps://www.nature.com/articles/s41436-019-0532-z
Arbitragem científicayes
AcessoAcesso restrito autor
Aparece nas coleções:ICVS - Artigos em revistas internacionais / Papers in international journals

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