Transcription profiling of human Hutchinson-Gilord progeria syndrome fibroblast cell lines with dominant mutation in the LMNA gene and age-matched normal controls

ABSTRACT: Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease with widespread phenotypic features resembling premature aging. HGPS was recently shown to be caused by dominant mutations in the LMNA gene, resulting in the in-frame deletion of 50 amino acids near the carboxyl terminus of the encoded lamin A protein. Children with this disease typically succumb to myocardial infarction or stroke caused by severe atherosclerosis at an average age of 13 years. To elucidate further the molecular; pathogenesis of this disease, we compared the gene expression patterns of three HGPS fibroblast cell lines heterozygous for the LMNA mutation with three normal, age-matched cell lines. We defined a set of 361 genes (1.1% of the approximately 33 000 genes analyzed) that showed at least a 2-fold, statistically significant change. The most prominent categories encode transcription factors and extracellular matrix proteins, many of which are known to function in the tissues severely affected in HGPS. The most affected gene, MEOX2/GAX, is a homeobox transcription factor implicated as a negative regulator of mesodermal tissue proliferation. Thus, at the gene expression level, HGPS shows the hallmarks of a developmental disorder affecting mesodermal and mesenchymal cell lineages. The identification of a large number of genes implicated in atherosclerosis is especially valuable, because it provides clues to pathological processes that can now be investigated in HGPS patients or animal models. Experiment Overall Design: Three fibroblast cell lines derived from HGPS patients were compared to three control fibroblast cell lines using Affymetrix HG-U133A and HG-133B probe arrays. Triplicates were used for each cell line. Total RNA was used in the analysis. Quantitation was done by MAS 5.0 software (Affymetrix).

ORGANISM(S): Homo sapiens

SUBMITTER: Sangeeta English 

PROVIDER: E-GEOD-3860 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress