Cerebellar degeneration-related protein 1 expression in fibroblasts of patients affected by down syndrome

Abstract

Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from lack of disjunction of sister chromatids of human chromosome 21 or not partial disjunction of chromosome 21 (Hsa21), usually during maternal meiosis. The expression of genes in chromosome 21 is very complex and many other genes in other chromosomes can play a role in DS. The protein encoded by the Cerebellar degeneration-related autoantigen 1 (CDR1) gene has been identified in patients with paraneoplastic cerebellar degeneration. Transcriptome studies show CDR1 expression in tumor cell lines and leukocytes of normal subjects and patients with Alzheimer's disease. We investigated CDR1 expression in cultured fibroblasts of DS patients compared with normal subjects. The study of CDR1 mRNA was performed with qRT-PCR. Immunofluorescence and Western blot were used for the analysis of the CDR1 protein. Our data show that both CDR1 mRNA and protein are expressed in human fibroblasts and that the CDR1 gene is down-regulated in DS fibroblasts compared to controls. These data suggest a role for CDR1 in DS phenotype.

KEYWORDS:

• Down syndrome
• intellectual disability
• CDR1 gene
• immunofluorescence
• Western blot
• qRT-PCR

Acknowledgements

Concept and Design done by Dr MS, Prof GR, Prof AEC, and Dr CR; Acquisition of data or analysis by Dr MS, Prof GR, Prof AEC, Dr CR, Dr MS, Dr FR, Dr R Can, Dr R Cas, Dr SC, Dr CT; Final approval by Dr CR, Dr MS, Prof AEC and Prof GR. All authors read and approved the final manuscript, and they have the accountability for all aspects of work. Consent for publication: All authors have consented the manuscript been published. Ethics approval and consent to participate: This study was approved by the Ethical Committee of the ‘IRCCS Associazione Oasi Maria SS.’, Troina (EN), Italy (2017/05/31/CE-IRCCS-OASI/9 of 3 June 2017). All the study participants signed an informed consent to publish.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by a fund from the Italian Ministry of Health ‘Ricerca Corrente’ (RC n. 2751604).