Somatic mutations in GLI3 and OFD1 involved in sonic hedgehog signaling cause hypothalamic hamartoma.

ABSTRACT:

Objective

Hypothalamic hamartoma (HH) is a congenital anomalous brain tumor. Although most HHs are found without any other systemic features, HH is observed in syndromic disorders such as Pallister-Hall syndrome (PHS) and oral-facial-digital syndrome (OFD). Here, we explore the possible involvement of somatic mutations in HH.

Methods

We analyzed paired blood and hamartoma samples from 18 individuals, including three with digital anomalies, by whole-exome sequencing. Detected somatic mutations were validated by Sanger sequencing and deep sequencing of target amplicons. The effect of GLI3 mutations on its transcriptional properties was evaluated by luciferase assays using reporters containing eight copies of the GLI-binding site and a mutated control sequence disrupting GLI bi

SUBMITTER: Saitsu H 

PROVIDER: S-EPMC4863748 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature