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.

Amati, F., Biancolella, M., D'Apice, M.r., Gambardella, S., Mango, R., Sbraccia, P., et al. (2004). Gene expression profiling of fibroblasts from a human progeroid disease mandibuloacral dysplasia, MAD #248370 through cDNA microarrays. GENE EXPRESSION, 12(1), 39-47.

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, SERGIO;SBRACCIA, PAOLO;D'ADAMO, MONICA;NOVELLI, GIUSEPPE
2004-01-01

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/09 - Medicina Interna
Settore MED/03 - Genetica Medica
English
Con Impact Factor ISI
Adolescent; Male; Syndrome; Oligonucleotide Array Sequence Analysis; Gene Expression Profiling; Female; Genes, Recessive; Dermis; Fibroblasts; Abnormalities, Multiple; Humans; Progeria; Mutation, Missense; Reverse Transcriptase Polymerase Chain Reaction; Lamins; Adult; Mandible; Lamin Type A
PMID: 15473259
Amati, F., Biancolella, M., D'Apice, M.r., Gambardella, S., Mango, R., Sbraccia, P., et al. (2004). Gene expression profiling of fibroblasts from a human progeroid disease mandibuloacral dysplasia, MAD #248370 through cDNA microarrays. GENE EXPRESSION, 12(1), 39-47.
Amati, F; Biancolella, M; D'Apice, Mr; Gambardella, S; Mango, R; Sbraccia, P; D'Adamo, M; Margiotti, K; Nardone, A; Lewis, M; Novelli, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/34797
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