A novel truncating variant of GLI2 associated with Culler-Jones syndrome impairs Hedgehog signalling.

ABSTRACT:

Background

GLI2 encodes for a transcription factor that controls the expression of several genes in the Hedgehog pathway. Mutations in GLI2 have been described as causative of a spectrum of clinical phenotypes, notably holoprosencephaly, hypopituitarism and postaxial polydactyl.

Methods

In order to identify causative genetic variant, we performed exome sequencing of a trio from an Italian family with multiple affected individuals presenting clinical phenotypes in the Culler-Jones syndrome spectrum. We performed a series of cell-based assays to test the functional properties of mutant GLI2.

Results

Here we report a novel deletion c.3493delC (p.P1167LfsX52) in the C-terminal activation domain of GLI2. Functional assays confirmed the pathogenicity of the identified varia

SUBMITTER: Valenza F 

PROVIDER: S-EPMC6328167 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature