The authors declare no conflict of interest.
Version of Record online: 13 JAN 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 2, pages 204–214, March 2011
How to Cite
Fullston, T., Gabb, B., Callen, D., Ullmann, R., Woollatt, E., Bain, S., Ropers, H. H., Cooper, M., Chandler, D., Carter, K., Jablensky, A., Kalaydjieva, L. and Gecz, J. (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., 156: 204–214. doi: 10.1002/ajmg.b.31157
How to Cite this Article: Fullston T, Gabb B, Callen D, Ullmann R, Woollatt E, Bain S, Ropers HH, Cooper1rter K, Jablensky A, Kalaydjieva L, Gecz J. 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 Part B 156: 204–214.
- Issue online: 8 FEB 2011
- Version of Record online: 13 JAN 2011
- Manuscript Accepted: 30 NOV 2010
- Manuscript Received: 12 AUG 2010
- Australian National Health and Medical Research Council
- balanced translocation t(9 ;17)(q33.2 ;q25.3);
- candidate gene;
- 16p13.1 duplication
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. © 2011 Wiley-Liss, Inc.