Publicação

Biallelic variants in the transcription factor PAX7 are a new genetic cause of myopathy

Detalhes bibliográficos
Resumo:	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.
Autores principais:	Feichtinger, René G.
Outros Autores:	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.
Assunto:	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 Ciências Médicas::Medicina Básica
Ano:	2019
País:	Portugal
Tipo de documento:	artigo
Tipo de acesso:	acesso restrito
Instituição associada:	Universidade do Minho
Idioma:	inglês
Origem:	RepositóriUM - Universidade do Minho