Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays

Francesca Amati, Michela Biancolella, Maria Rosaria D'Apice, Stefano Gambardella, Ruggiero Mango, Paolo Sbraccia, Monica D'Adamo, Katia Margiotti, Annamaria Nardone, Marc Lewis, Giuseppe Novelli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)39-47
Number of pages9
JournalGene Expression
Volume12
Issue number1
Publication statusPublished - 2004

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Gene Expression Profiling
Oligonucleotide Array Sequence Analysis
Fibroblasts
Genes
Mutation
Dermis
Lamin Type A
Biological Phenomena
Expressed Sequence Tags
Missense Mutation
Cell Adhesion
Cell Cycle
Polymerase Chain Reaction

Keywords

  • Lamin A/C
  • Mandibuloacral dysplasia
  • Microarray
  • QRT-PCR

ASJC Scopus subject areas

  • Genetics

Cite this

Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays. / Amati, Francesca; Biancolella, Michela; D'Apice, Maria Rosaria; Gambardella, Stefano; Mango, Ruggiero; Sbraccia, Paolo; D'Adamo, Monica; Margiotti, Katia; Nardone, Annamaria; Lewis, Marc; Novelli, Giuseppe.

In: Gene Expression, Vol. 12, No. 1, 2004, p. 39-47.

Research output: Contribution to journalArticle

Amati, F, Biancolella, M, D'Apice, MR, Gambardella, S, Mango, R, Sbraccia, P, D'Adamo, M, Margiotti, K, Nardone, A, Lewis, M & Novelli, G 2004, 'Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays', Gene Expression, vol. 12, no. 1, pp. 39-47.
Amati, Francesca ; Biancolella, Michela ; D'Apice, Maria Rosaria ; Gambardella, Stefano ; Mango, Ruggiero ; Sbraccia, Paolo ; D'Adamo, Monica ; Margiotti, Katia ; Nardone, Annamaria ; Lewis, Marc ; Novelli, Giuseppe. / Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays. In: Gene Expression. 2004 ; Vol. 12, No. 1. pp. 39-47.
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