Gene expression profiling of hypothalamic hamartomas: A search for genes associated with central precocious puberty

Background: Hypothalamic hamartomas (HHs) are congenital lesions composed of neurons and astroglia. Frequently, HHs cause central precocious puberty (CPP) and/or gelastic seizures. Because HHs might express genes similar to those required for the initiation of normal puberty, we used cDNA arrays to compare the gene expression profile of an HH associated with CPP with three HHs not accompanied by sexual precocity. Methods: Global changes in gene expression were detected using Affymetrix arrays. The results were confirmed by semiquantitative PCR, which also served to examine the expression of selected genes in the hypothalamus of female monkeys undergoing puberty. Results: All HHs were associated with seizures. Ten genes whose expression was increased in the HH with CPP were identified. They encode proteins involved in three key cellular processes: transcriptional regulation, cell-cell signaling, and cell adhesiveness. They include IA-1 and MEF2A, two transcription factors required for neuronal development; mGluR1 and VILIP-1, which encode proteins involved in neuronal communication, and TSG-6 that encodes a protein involved in cell adhesiveness. Of these, expression of mGluR1 also increases in the female monkey hypothalamus at puberty. Conclusions: Increased expression of these genes in HHs may be relevant to the ability of some HHs to induce sexual precocity.