Gene expression profiling of fibroblasts from a human progeroid disease (mandibuloacral dysplasia, MAD #248370) through cDNA microarrays.
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
Francesca
F
Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Via Montpellier 1, 00133 Roma, Italy.
Biancolella
Michela
M
D'Apice
Maria Rosaria
MR
Gambardella
Stefano
S
Mango
Ruggiero
R
Sbraccia
Paolo
P
D'Adamo
Monica
M
Margiotti
Katia
K
Nardone
Annamaria
A
Lewis
Marc
M
Novelli
Giuseppe
G
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D020405:Dermis / Q000378:metabolism; D005260:Female; D005347:Fibroblasts; D020869:Gene Expression Profiling; D005808:Genes, Recessive; D006801:Humans; D034904:Lamin Type A; D034882:Lamins / Q000235:genetics; D008297:Male; D008334:Mandible / Q000002:abnormalities*; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011371:Progeria / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome
C494847:LMNA protein, human; D034904:Lamin Type A; D034882:Lamins