Elucidating the impact of neurofibromatosis-1 germline mutations on neurofibromin function and dopamine-based learning.

ABSTRACT: Neurofibromatosis type 1 (NF1) is a common autosomal dominant neurologic condition characterized by significant clinical heterogeneity, ranging from malignant cancers to cognitive deficits. Recent studies have begun to reveal rare genotype-phenotype correlations, suggesting that the specific germline NF1 gene mutation may be one factor underlying disease heterogeneity. The purpose of this study was to define the impact of the germline NF1 gene mutation on brain neurofibromin function relevant to learning. Herein, we employ human NF1-patient primary skin fibroblasts, induced pluripotent stem cells and derivative neural progenitor cells (NPCs) to demonstrate that NF1 germline mutations have dramatic effects on neurofibromin expression. Moreover, while all NF1-patient NPCs exhibit increased R

SUBMITTER: Anastasaki C 

PROVIDER: S-EPMC4553714 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature