You are here: Home Publications De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

de Lange, I. M., Helbig, K. L., Weckhuysen, S., Moller, R. S., Velinov, M., Dolzhanskaya, N., Marsh, E., Helbig, I., Devinsky, O., Tang, S., Mefford, H. C., Myers, C. T., van Paesschen, W., Striano, P., van Gassen, K., van Kempen, M., De Kovel, C. G. F., Piard, J., Minassian, B. A., Nezarati, M. M., Pessoa, A., Jacquette, A., Maher, B., Balestrini, S., Sisodiya, S., Warde, M. T., De St Martin, A., Chelly, J., van 't Slot, R., Van Maldergem, L., Brilstra, E. H., & Koeleman, B. P. (2016). De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy. Journal of Medical Genetics. Advance online publication. doi:10.1136/jmedgenet-2016-103909.
Background Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy. Methods Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible. Results All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X-inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles. Conclusions Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy.
About MPI

This is the MPI

The Max Planck Institute for Psycholinguistics is an institute of the German Max Planck Society. Our mission is to undertake basic research into the psychological,social and biological foundations of language. The goal is to understand how our minds and brains process language, how language interacts with other aspects of mind, and how we can learn languages of quite different types.

The institute is situated on the campus of the Radboud University. We participate in the Donders Institute for Brain, Cognition and Behaviour, and have particularly close ties to that institute's Centre for Cognitive Neuroimaging. We also participate in the Centre for Language Studies. A joint graduate school, the IMPRS in Language Sciences, links the Donders Institute, the CLS and the MPI.


Street address
Wundtlaan 1
6525 XD Nijmegen
The Netherlands

Mailing address
P.O. Box 310
6500 AH Nijmegen
The Netherlands

Phone:   +31-24-3521911
Fax:        +31-24-3521213

Public Outreach Officer
Charlotte Horn