Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans.

ABSTRACT:

Background

Autophagy is the major intracellular degradation route in mammalian cells. Systemic ablation of core autophagy-related (ATG) genes in mice leads to embryonic or perinatal lethality, and conditional models show neurodegeneration. Impaired autophagy has been associated with a range of complex human diseases, yet congenital autophagy disorders are rare.

Methods

We performed a genetic, clinical, and neuroimaging analysis involving five families. Mechanistic investigations were conducted with the use of patient-derived fibroblasts, skeletal muscle-biopsy specimens, mouse embryonic fibroblasts, and yeast.

Results

We found deleterious, recessive variants in human ATG7, a core autophagy-related gene encoding a protein that is indispensable to classica

SUBMITTER: Collier JJ 

PROVIDER: S-EPMC7611730 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature