Open Access Open Badges Research article

Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy

Anna Conti1, Floriana Fabbrini12, Paola D'Agostino2, Rosa Negri1, Dario Greco3, Rita Genesio12, Maria D'Armiento4, Carlo Olla4, Dario Paladini5, Mariastella Zannini6 and Lucio Nitsch12*

  • * Corresponding author: Lucio Nitsch

  • † Equal contributors

Author Affiliations

1 Dipartimento di Biologia e Patologia Cellulare e Molecolare, University Federico II, Napoli, Italy

2 BIOGEM, Biotechnology and Molecular Genetics, Italy

3 Institute of Biotechnology, University of Helsinki, Finland

4 Dipartimento di Scienze Biomorfologiche e Funzionali, University Federico II, Napoli, Italy

5 Dipartimento di Scienze Ostetriche, Ginecologiche ed Urologiche e Fisiopatologia della Riproduzione, University Federico II, Napoli, Italy

6 Istituto di Endocrinologia ed Oncologia Sperimentale (IEOS) del CNR, Napoli, Italy

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BMC Genomics 2007, 8:268  doi:10.1186/1471-2164-8-268

Published: 7 August 2007



The Down syndrome phenotype has been attributed to overexpression of chromosome 21 (Hsa21) genes. However, the expression profile of Hsa21 genes in trisomic human subjects as well as their effects on genes located on different chromosomes are largely unknown. Using oligonucleotide microarrays we compared the gene expression profiles of hearts of human fetuses with and without Hsa21 trisomy.


Approximately half of the 15,000 genes examined (87 of the 168 genes on Hsa21) were expressed in the heart at 18–22 weeks of gestation. Hsa21 gene expression was globally upregulated 1.5 fold in trisomic samples. However, not all genes were equally dysregulated and 25 genes were not upregulated at all. Genes located on other chromosomes were also significantly dysregulated. Functional class scoring and gene set enrichment analyses of 473 genes, differentially expressed between trisomic and non-trisomic hearts, revealed downregulation of genes encoding mitochondrial enzymes and upregulation of genes encoding extracellular matrix proteins. There were no significant differences between trisomic fetuses with and without heart defects.


We conclude that dosage-dependent upregulation of Hsa21 genes causes dysregulation of the genes responsible for mitochondrial function and for the extracellular matrix organization in the fetal heart of trisomic subjects. These alterations might be harbingers of the heart defects associated with Hsa21 trisomy, which could be based on elusive mechanisms involving genetic variability, environmental factors and/or stochastic events.