Biallelic variants in the transcription factor PAX7 are a new genetic cause of myopathy.
Genet Med
; 21(11): 2521-2531, 2019 11.
Article
en En
| MEDLINE
| ID: mdl-31092906
ABSTRACT
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factor de Transcripción PAX7
/
Enfermedades Musculares
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2019
Tipo del documento:
Article