A homozygous MED11 C-terminal variant causes a lethal neurodegenerative disease.

ABSTRACT:

Purpose

The mediator (MED) multisubunit-complex modulates the activity of the transcriptional machinery, and genetic defects in different MED subunits (17, 20, 27) have been implicated in neurologic diseases. In this study, we identified a recurrent homozygous variant in MED11 (c.325C>T; p.Arg109Ter) in 7 affected individuals from 5 unrelated families.

Methods

To investigate the genetic cause of the disease, exome or genome sequencing were performed in 5 unrelated families identified via different research networks and Matchmaker Exchange. Deep clinical and brain imaging evaluations were performed by clinical pediatric neurologists and neuroradiologists. The functional effect of the candidate variant on both MED11 RNA and protein was assessed using reverse transcriptase poly

SUBMITTER: Cali E 

PROVIDER: S-EPMC10519206 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature