Bi-allelic ATG4D variants are associated with a neurodevelopmental disorder characterized by speech and motor impairment.

ABSTRACT: Autophagy regulates the degradation of damaged organelles and protein aggregates, and is critical for neuronal development, homeostasis, and maintenance, yet few neurodevelopmental disorders have been associated with pathogenic variants in genes encoding autophagy-related proteins. We report three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment, and similar facial characteristics. Rare, conserved, bi-allelic variants were identified in ATG4D, encoding one of four ATG4 cysteine proteases important for autophagosome biogenesis, a hallmark of autophagy. Autophagosome biogenesis and induction of autophagy were intact in cells from affected individuals. However, studies evaluating the predominant substrate of ATG4D, GABARAP

SUBMITTER: Morimoto M 

PROVIDER: S-EPMC9918471 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature