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  Inherited balanced translocation t(9;17)(q33.2;q25.3) concomitant with a 16p13.1 duplication in a patient with schizophrenia

Fullston, T., Gabb, B., Callen, D., Ullmann, R., Woollatt, E., Bain, S., et al. (2011). Inherited balanced translocation t(9;17)(q33.2;q25.3) concomitant with a 16p13.1 duplication in a patient with schizophrenia. Am J Med Genet B Neuropsychiatr Genet, 156(2), 204-14. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21302349 http://onlinelibrary.wiley.com/store/10.1002/ajmg.b.31157/asset/31157_ftp.pdf?v=1&t=gywok64d&s=96b296da76b137802fd0adf3d9c678b4a01464af.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-796B-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-796C-7
Genre: Journal Article

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Fullston, T., Author
Gabb, B., Author
Callen, D., Author
Ullmann, R.1, Author              
Woollatt, E., Author
Bain, S., Author
Ropers, H. H.2, Author              
Cooper, M., Author
Chandler, D., Author
Carter, K., Author
Jablensky, A., Author
Kalaydjieva, L., Author
Gecz, J., Author
Affiliations:
1Molecular Cytogenetics (Reinhard Ullmann), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479645              
2Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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Free keywords: Adult; Alleles; *Chromosomes, Human, Pair 16; Chromosomes, Human, Pair 17/*genetics; Chromosomes, Human, Pair 9/*genetics; Family; Humans; Male; Mutation/genetics; Nerve Tissue Proteins/genetics; Pedigree; Protein Processing, Post-Translational; Schizophrenia/*genetics/metabolism/pathology; *Segmental Duplications, Genomic; *Translocation, Genetic
 Abstract: We report two rare genetic aberrations in a schizophrenia patient that may act together to confer disease susceptibility. A previously unreported balanced t(9;17)(q33.2;q25.3) translocation was observed in two schizophrenia-affected members of a small family with diverse psychiatric disorders. The proband also carried a 1.5 Mbp microduplication at 16p13.1 that could not be investigated in other family members. The duplication has been reported to predispose to schizophrenia, autism and mental retardation, with incomplete penetrance and variable expressivity. The t(9;17) (q33.2;q25.3) translocation breakpoint occurs within the open reading frames of KIAA1618 on 17q25.3, and TTLL11 (tyrosine tubulin ligase like 11) on 9q33.2, causing no change in the expression level of KIAA1618 but leading to loss of expression of one TTLL11 allele. TTLL11 belongs to a family of enzymes catalyzing polyglutamylation, an unusual neuron-specific post-translational modification of microtubule proteins, which modulates microtubule development and dynamics. The 16p13.1 duplication resulted in increased expression of NDE1, encoding a DISC1 protein partner mediating DISC1 functions in microtubule dynamics. We hypothesize that concomitant TTLL11-NDE1 deregulation may increase mutation load, among others, also on the DISC1 pathway, which could contribute to disease pathogenesis through multiple effects on neuronal development, synaptic plasticity, and neurotransmission. Our data illustrate the difficulties in interpreting the contribution of multiple potentially pathogenic changes likely to emerge in future next-generation sequencing studies, where access to extended families will be increasingly important.

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 Dates: 2011
 Publication Status: Published in print
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Title: Am J Med Genet B Neuropsychiatr Genet
Source Genre: Journal
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Pages: - Volume / Issue: 156 (2) Sequence Number: - Start / End Page: 204 - 14 Identifier: ISSN: 1552-485X (Electronic) 1552-4841 (Linking)