Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111071
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Abnormal cell sorting underlies the unique X-linked inheritance of PCDH19 epilepsy
Author: Pederick, D.
Richards, K.
Piltz, S.
Kumar, R.
Mincheva-Tasheva, S.
Mandelstam, S.
Dale, R.
Scheffer, I.
Gecz, J.
Petrou, S.
Hughes, J.
Thomas, P.
Citation: Neuron, 2018; 97(1):59-e5
Publisher: CELL PRESS
Issue Date: 2018
ISSN: 0896-6273
1097-4199
Statement of
Responsibility: 
Daniel T. Pederick, Kay L. Richards, Sandra G. Piltz, Raman Kumar, Stefka Mincheva-Tasheva, Simone A. Mandelstam, Russell C. Dale, Ingrid E. Scheffer, Jozef Gecz, Steven Petrou, James N. Hughes and Paul Q. Thomas
Abstract: X-linked diseases typically exhibit more severe phenotypes in males than females. In contrast, protocadherin 19 (PCDH19) mutations cause epilepsy in heterozygous females but spare hemizygous males. The cellular mechanism responsible for this unique pattern of X-linked inheritance is unknown. We show that PCDH19 contributes to adhesion specificity in a combinatorial manner such that mosaic expression of Pcdh19 in heterozygous female mice leads to striking sorting between cells expressing wild-type (WT) PCDH19 and null PCDH19 in the developing cortex, correlating with altered network activity. Complete deletion of PCDH19 in heterozygous mice abolishes abnormal cell sorting and restores normal network activity. Furthermore, we identify variable cortical malformations in PCDH19 epilepsy patients. Our results highlight the role of PCDH19 in determining cell adhesion affinities during cortical development and the way segregation of WT and null PCDH19 cells is associated with the unique X-linked inheritance of PCDH19 epilepsy.
Keywords: PCDH19-GCE; cell sorting
Rights: © 2017 Elsevier Inc.
RMID: 0030079914
DOI: 10.1016/j.neuron.2017.12.005
Grant ID: http://purl.org/au-research/grants/nhmrc/400121
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.