Abstract
Andersen–Tawil syndrome (ATS) is a rare familial potassium channelopathy characterized by the clinical triad of periodic paralysis, cardiac arrhythmia and dysmorphic facial/skeletal features. The majority of ATS patients are caused by mutations of the KCNJ2 gene, which encodes the inward-rectifying potassium channel protein Kir2.1. However, the effects of the KCNJ2 mutation on the central nervous system are rarely studied. In this report, we describe a heterozygous missense mutation (p.Thr192Ile) in the KCNJ2 gene, which segregates with the disease phenotype in an ATS family. It is noted that in addition to the classical clinical phenotypes of ATS, the index patient exhibited major depression and pyramidal tract signs with diffuse periventricular white matter lesions without contrast enhancement. This mutation and the unusual clinical manifestations observed underscore the phenotypic complexity underlying ATS. Our observations expand the current knowledge of the phenotypic variability of ATS caused by the KCNJ2 mutation. Patients with ATS, especially those carrying the KCNJ2 mutations, should be monitored for their potential neuropsychiatric system involvement.
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References
Andersen, E. D., Krasilnikoff, P. A. & Overvad, H. Intermittent muscular weakness, extrasystoles, and multiple developmental anomalies. A new syndrome? Acta. Paediatr. Scand. 60, 559–564 (1971).
Plaster, N. M., Tawil, R., Tristani-Firouzi, M., Canun, S., Bendahhou, S., Tsunoda, A. et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 105, 511–519 (2001).
Patil, N., Cox, D. R., Bhat, D., Faham, M., Myers, R. M. & Peterson, A. S. A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation. Nat. Genet. 11, 126–129 (1995).
Yoon, G., Quitania, L., Kramer, J. H., Fu, Y. H., Miller, B. L. & Ptacek, L. J. Andersen-Tawil syndrome: definition of a neurocognitive phenotype. Neurology 66, 1703–1710 (2006).
Haruna, Y., Kobori, A., Makiyama, T., Yoshida, H., Akao, M., Doi, T. et al. Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome. Hum. Mutat. 28, 208–220 (2007).
Gmitrowicz, A. & Kucharska, A. Developmental disorders in the fourth edition of the American classification: diagnostic and statistical manual of mental disorders (DSM IV—optional book). Psychiatr. Pol. 28, 509–521 (1994).
Hosaka, Y., Hanawa, H., Washizuka, T., Chinushi, M., Yamashita, F., Yoshida, T. et al. Function, subcellular localization and assembly of a novel mutation of KCNJ2 in Andersen's syndrome. J. Mol. Cell Cardiol. 35, 409–415 (2003).
Davies, N. P., Imbrici, P., Fialho, D., Herd, C., Bilsland, L. G., Weber, A. et al. Andersen-Tawil syndrome: new potassium channel mutations and possible phenotypic variation. Neurology 65, 1083–1089 (2005).
Sooma, M., Schönherra, R., Kubob, Y., Kirschc, C., Klingerc, R. & Heinemanna, S. H. Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels. FEBS Lett. 490, 49–53 (2001).
Sansone, V. & Tawil, R. Management and treatment of Andersen-Tawil syndrome (ATS). Neurotherapeutics 4, 233–237 (2007).
Neusch, C., Weishaupt, J. H. & Bahr, M. Kir channels in the CNS: emerging new roles and implications for neurological diseases. Cell Tissue Res. 311, 131–138 (2003).
Kalsi, A. S., Greenwood, K., Wilkin, G. & Butt, A. M. Kir4.1 expression by astrocytes and oligodendrocytes in CNS white matter: a developmental study in the rat optic nerve. J. Anat. 204, 475–485 (2004).
Zaritsky, J. J., Eckman, D. M., Wellman, G. C., Nelson, M. T. & Schwarz, T. L. Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)-mediated vasodilation. Circ. Res. 87, 160–166 (2000).
Walz, W. Chloride/anion channels in glial cell membranes. Glia 40, 1–10 (2002).
Neusch, C., Rozengurt, N., Jacobs, R. E., Lester, H. A. & Kofuji, P. Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J. Neurosci. 21, 5429–5438 (2001).
Acknowledgements
We thank the patients who have participated in this study and the staff of the Second Core Lab, Department of Medical Research of National Taiwan University Hospital, for technical support during the study.
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Chan, HF., Chen, ML., Su, JJ. et al. A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen–Tawil syndrome. J Hum Genet 55, 186–188 (2010). https://doi.org/10.1038/jhg.2010.2
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DOI: https://doi.org/10.1038/jhg.2010.2
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