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Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation

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Abstract

Mental retardation (MR) is displayed by 57% of NF1 patients with microdeletion syndrome as a result of 17q11.2 region haploinsufficiency. We considered the cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) and oligodendrocyte-myelin glycoprotein (OMG) genes, mapping in the NF1 microdeleted region, as candidate genes for MR susceptibility. CDK5R1 encodes for a neurone-specific activator of cyclin-dependent kinase 5 (CDK5) involved in neuronal migration during central nervous system development. OMG encodes for an inhibitor of neurite outgrowth by the binding to the Nogo-66 receptor (RTN4R). CDK5R1 and OMG genes are characterized by large 3′ and 5′ untranslated regions (UTRs), where we predict the presence of several transcription/translation regulatory elements. We screened 100 unrelated Italian patients affected by unspecific MR for mutations in CDK5R1 and OMG coding regions and in their 3′ or 5′ UTRs. Four novel mutations and two novel polymorphisms for CDK5R1 and three novel mutations for OMG were detected, including two missense changes (c.323C>T; A108V in CDK5R1 and c.1222A>G; T408A in OMG), one synonymous codon variant (c.532C>T; L178L in CDK5R1), four variants in CDK5R1 3′UTR and two changes in OMG 5′UTR. All the mutations were absent in 370 chromosomes from normal subjects. The allelic frequencies of the two novel polymorphisms in CDK5R1 3′UTR were established in both 185 normal and 100 mentally retarded subjects. Prediction of mRNA and protein secondary structures revealed that two changes lead to putative structural alterations in the mutated c.2254C>G CDK5R1 3′UTR and in OMG T408A gene product.

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Acknowledgements

The authors thank Professor Graziano Pesole (Department of Biomolecular Sciences and Biotechnology, University of Milan) for his helpful suggestions on UTR regulatory elements searching, Elena Gismano and Rosina Paterra fo their technical support. This work was supported by FIRST to PR.

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Authors and Affiliations

  1. Department of Biology and Genetics, Medical Faculty, University of Milan, Via Viotti 3/5, 20133, Milan, Italy

    Marco Venturin, Silvia Moncini, Valentina Villa, Lidia Larizza & Paola Riva

  2. Laboratory of Medical Cytogenetics and Molecular Genetics, Istituto Auxologico Italiano, Milan, Italy

    Silvia Russo, Maria Teresa Bonati & Lidia Larizza

Authors
  1. Marco Venturin
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  2. Silvia Moncini
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  3. Valentina Villa
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  4. Silvia Russo
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  5. Maria Teresa Bonati
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  6. Lidia Larizza
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  7. Paola Riva
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Correspondence to Paola Riva.

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M. Venturin and S. Moncini equally contributed to this work.

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Venturin, M., Moncini, S., Villa, V. et al. Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation. Neurogenetics 7, 59–66 (2006). https://doi.org/10.1007/s10048-005-0026-9

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