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Feichtinger, R.G.* ; Mucha, B.E.* ; Hengel, H.* ; Orfi, Z.* ; Makowski, C.* ; Dort, J.* ; D'Anjou, G.* ; Nguyen, T.T.M.* ; Buchert, R.* ; Juenger, H.* ; Freisinger, P.* ; Baumeister, S.* ; Schoser, B.* ; Ahting, U.* ; Keimer, R.* ; Nguyen, C.E.* ; Fabre, P.* ; Gauthier, J.* ; Miguet, M.* ; Lopes, F.* ; AlHakeem, A.* ; Alhashem, A.* ; Tabarki, B.* ; Kandaswamy, K.K.* ; Bauer, P.* ; Steinbacher, P.* ; Prokisch, H. ; Sturm, M.* ; Strom, T.M. ; Ellezam, B.* ; Mayr, J.A.* ; Schöls, L.* ; Michaud, J.L.* ; Campeau, P.M.* ; Haack, T.B.* ; Dumont, N.A.*

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

Genet. Med. 21, 2521-2531 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Muscle Stem Cell ; Myoblasts ; Myopathy ; Pax7 ; Skeletal Muscle
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 1530-0366
e-ISSN 1098-3600
Zeitschrift Genetics in Medicine
Quellenangaben Band: 21, Heft: 11, Seiten: 2521-2531 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Baltimore, Md.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
DOI 10.1038/s41436-019-0532-z
Scopus ID 85065997521
PubMed ID 31092906
Erfassungsdatum 2019-05-20
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