Homozygous boricua TBCK mutation causes neurodegeneration and aberrant autophagy.

ABSTRACT:

Objective

Autosomal-recessive mutations in TBCK cause intellectual disability of variable severity. Although the physiological function of TBCK remains unclear, loss-of-function mutations are associated with inhibition of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Given that mTORC1 signaling is known to regulate autophagy, we hypothesized that TBCK-encephalopathy patients with a neurodegenerative course have defects in autophagic-lysosomal dysfunction.

Methods

Children (n = 8) of Puerto Rican (Boricua) descent affected with homozygous TBCK p.R126X mutations underwent extensive neurological phenotyping and neurophysiological studies. We quantified autophagosome content in TBCK^-/- patient-derived fibroblasts by immunostaining and assayed autophagi

SUBMITTER: Ortiz-Gonzalez XR 

PROVIDER: S-EPMC5876123 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature