Back to Search
Start Over
Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays.
- Source :
-
Gene expression [Gene Expr] 2004; Vol. 12 (1), pp. 39-47. - Publication Year :
- 2004
-
Abstract
- Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder caused basically by a missense mutation within the LMNA gene, which encodes for lamin A/C. We have used gene expression profiling to characterize the specificity of molecular changes induced by the prevalent MAD mutation (R527H). A total of 5531 transcripts expressed in human dermis were investigated in two MAD patients, both carrying the R527H mutation, and three control subjects (age and sex matched). Transcription profiles revealed a differential expression in MAD vs. control fibroblasts in at least 1992 genes. Sixty-seven of these genes showed a common altered pattern in both patients with a threshold expression level >+/-2. Nevertheless, a large number of these genes (43.3%) are ESTs or encode for protein with unknown function; the other genes are involved in biological processes or pathways such as cell adhesion, cell cycle, cellular metabolism, and transcription. Quantitative RT-PCR was applied to validate the microarray results (R2= 0.76). Analysis of the effect of the prevalent MAD mutation (R527H) over the transcriptional pattern of genes expressed in the human dermis showed that this LMNA gene mutation has pleiotropic effects on a limited number of genes. Further characterization of these effects might contribute to understanding the molecular pathogenesis of this disorder.
- Subjects :
- Adolescent
Adult
Dermis metabolism
Female
Fibroblasts
Genes, Recessive
Humans
Lamin Type A
Lamins genetics
Male
Mutation, Missense
Reverse Transcriptase Polymerase Chain Reaction
Syndrome
Abnormalities, Multiple genetics
Gene Expression Profiling
Mandible abnormalities
Oligonucleotide Array Sequence Analysis methods
Progeria genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1052-2166
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Gene expression
- Publication Type :
- Academic Journal
- Accession number :
- 15473259
- Full Text :
- https://doi.org/10.3727/000000004783992189