Open Access Research article

Genome-wide expression profiling and functional characterization of SCA28 lymphoblastoid cell lines reveal impairment in cell growth and activation of apoptotic pathways

Cecilia Mancini1, Paola Roncaglia23, Alessandro Brussino1, Giovanni Stevanin456, Nicola Lo Buono1, Helena Krmac3, Francesca Maltecca7, Elena Gazzano8, Anna Bartoletti Stella9, Maria Antonietta Calvaruso1011, Luisa Iommarini10, Claudia Cagnoli1, Sylvie Forlani4, Isabelle Le Ber4, Alexandra Durr45, Alexis Brice45, Dario Ghigo8, Giorgio Casari7, Anna Maria Porcelli10, Ada Funaro1, Giuseppe Gasparre9, Stefano Gustincich3 and Alfredo Brusco111*

Author Affiliations

1 Department of Medical Sciences, University of Torino, via Santena 19, 10126 Torino, Italy

2 European Bioinformatics Institute, Cambridge, UK

3 Neurobiology Sector, SISSA/ISAS, Trieste, Italy

4 Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière (INSERM / UPMC Univ. Paris 6, UMR_S975 ; CNRS 7225), Pitié-Salpêtrière Hospital, Paris, France

5 APHP, Fédération de génétique, Pitié-Salpêtrière Hospital, Paris, France

6 Neurogenetics team, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle épinière, CHU Pitié-Salpêtrière, Paris, France

7 San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, Milan-I, Italy

8 Department of Oncology, University of Torino, Candiolo, Italy

9 Department Medical and Surgical Sciences, Medical Genetics, University of Bologna, Bologna, Italy

10 Department of Pharmacy and Biotechnologies (FABIT), University of Bologna, Bologna, Italy

11 Medical Genetics Unit, “Città della Salute e della Scienza” Hospital, Torino, Italy

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BMC Medical Genomics 2013, 6:22  doi:10.1186/1755-8794-6-22

Published: 18 June 2013



SCA28 is an autosomal dominant ataxia associated with AFG3L2 gene mutations. We performed a whole genome expression profiling using lymphoblastoid cell lines (LCLs) from four SCA28 patients and six unrelated healthy controls matched for sex and age.


Gene expression was evaluated with the Affymetrix GeneChip Human Genome U133A 2.0 Arrays and data were validated by real-time PCR.


We found 66 genes whose expression was statistically different in SCA28 LCLs, 35 of which were up-regulated and 31 down-regulated. The differentially expressed genes were clustered in five functional categories: (1) regulation of cell proliferation; (2) regulation of programmed cell death; (3) response to oxidative stress; (4) cell adhesion, and (5) chemical homeostasis. To validate these data, we performed functional experiments that proved an impaired SCA28 LCLs growth compared to controls (p < 0.005), an increased number of cells in the G0/G1 phase (p < 0.001), and an increased mortality because of apoptosis (p < 0.05). We also showed that respiratory chain activity and reactive oxygen species levels was not altered, although lipid peroxidation in SCA28 LCLs was increased in basal conditions (p < 0.05). We did not detect mitochondrial DNA large deletions. An increase of TFAM, a crucial protein for mtDNA maintenance, and of DRP1, a key regulator of mitochondrial dynamic mechanism, suggested an alteration of fission/fusion pathways.


Whole genome expression profiling, performed on SCA28 LCLs, allowed us to identify five altered functional categories that characterize the SCA28 LCLs phenotype, the first reported in human cells to our knowledge.

Autosomal dominant cerebellar ataxia; Spinocerebellar ataxia; SCA28; AFG3L2; Genome-wide expression; LCLs