Exome sequencing reveals germline gain-of-function <i>EGFR</i> mutation in an adult with Lhermitte-Duclos disease.

ABSTRACT: Lhermitte-Duclos disease (LDD) is a rare cerebellar disorder believed to be pathognomonic for Cowden syndrome. Presently, the only known etiology is germline PTEN mutation. We report a 41-yr-old white female diagnosed with LDD and wild-type for PTEN. Exome sequencing revealed a germline heterozygous EGFR mutation that breaks a disulfide bond in the receptor's extracellular domain, resulting in constitutive activation. Functional studies demonstrate activation of ERK/AKT signaling pathways, mimicking PTEN loss-of-function downstream effects. The identification of EGFR as a candidate LDD susceptibility gene contributes to advancement of molecular diagnosis and targeted therapy for this rare condition with limited treatment options.

SUBMITTER: Colby S 

PROVIDER: S-EPMC5111001 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature