CDK5 and its activator p35, encoded by CDK5R1 gene, are highly expressed in CNS where they have a fundamental role in neuronal migration and differentiation during CNS development. Their fundamental role in CNS development and function, and their involvement in the pathogenesis of neurodegenerative disorders makes CDK5 and CDK5R1 strong candidate genes for the onset of mental retardation. We carried out the mutation screening of CDK5 and CDK5R1 coding regions, as well as of CDK5R1 3’-UTR, on a cohort of 344 patients with non-syndromic mental retardation (NS-MR). In fact, we recently demonstrated that 3’-UTR has a key role in the post-transcriptional regulation of CDK5R1 expression, through the binding of protein factors and microRNAs belonging to miR-15/107 family, and this evidence prompted us to include this region in the mutational analysis. We found one silent mutation in CDK5, and three silent and two missense conservative mutations in CDK5R1 coding region. Four novel variations in intronic regions of CDK5 were also found but never predicted to cause splicing defects. Interestingly, we found nine heterozygous variations in CDK5R1 3’-UTR: among these, six were single base substitutions and three were small deletions. None of these variations was present in 450 healthy controls. Of particular interest is the deletion of one predicted miR-15/107 family binding site, found in one patient. Luciferase constructs containing the mutations observed in CDK5R1 3’-UTR will be used to verify if these variations have an effect on CDK5R1 expression levels and therefore constitute susceptibility variants for NS-MR

Extensive mutational analysis of CDK5 and CDK5R1 in patients with non-syndromic mental retardation reveals novel variants in CDK5R1 3’-UTR / S. Moncini, P. Castronovo, A. Murgia, S. Russo, M.F. Bedeschi, P. Riva, M. Venturin. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - 20:Suppl.1(2012), pp. 399-399. ((Intervento presentato al convegno European Human Genetics Conference in conjunction with the European Meeting on Psychosocial Aspects of Genetics and the German Society of Human Genetics tenutosi a Nürnberg nel 2012.

Extensive mutational analysis of CDK5 and CDK5R1 in patients with non-syndromic mental retardation reveals novel variants in CDK5R1 3’-UTR

S. Moncini
Primo
;
P. Castronovo
Secondo
;
P. Riva
Penultimo
;
M. Venturin
Ultimo
2012

Abstract

CDK5 and its activator p35, encoded by CDK5R1 gene, are highly expressed in CNS where they have a fundamental role in neuronal migration and differentiation during CNS development. Their fundamental role in CNS development and function, and their involvement in the pathogenesis of neurodegenerative disorders makes CDK5 and CDK5R1 strong candidate genes for the onset of mental retardation. We carried out the mutation screening of CDK5 and CDK5R1 coding regions, as well as of CDK5R1 3’-UTR, on a cohort of 344 patients with non-syndromic mental retardation (NS-MR). In fact, we recently demonstrated that 3’-UTR has a key role in the post-transcriptional regulation of CDK5R1 expression, through the binding of protein factors and microRNAs belonging to miR-15/107 family, and this evidence prompted us to include this region in the mutational analysis. We found one silent mutation in CDK5, and three silent and two missense conservative mutations in CDK5R1 coding region. Four novel variations in intronic regions of CDK5 were also found but never predicted to cause splicing defects. Interestingly, we found nine heterozygous variations in CDK5R1 3’-UTR: among these, six were single base substitutions and three were small deletions. None of these variations was present in 450 healthy controls. Of particular interest is the deletion of one predicted miR-15/107 family binding site, found in one patient. Luciferase constructs containing the mutations observed in CDK5R1 3’-UTR will be used to verify if these variations have an effect on CDK5R1 expression levels and therefore constitute susceptibility variants for NS-MR
Settore BIO/13 - Biologia Applicata
European Society of Human Genetics
German Society of Human Genetics
https://www.eshg.org/fileadmin/www.eshg.org/conferences/2012/ESHG2012Abstracts.pdf
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/199916
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