TY - JOUR
T1 - Disentangling the paradox of the PCDH19 clustering epilepsy, a disorder of cellular mosaics
AU - Gecz, Jozef
AU - Thomas, Paul Q.
N1 - Funding Information:
We would like to thank Raman Kumar for critical reading of the manuscript and Kristy Kolc for help with data for Figure 1 b. We apologise to colleagues whose work we were unable to cite due to space constraints. Our work has been supported by an NHMRC fellowship APP1155224 and Program Grant APP1091593 to J.G., a Channel 7 Children’s Research Foundation grant to J.G., an NHMRC Project grant APP1188520 to P.T. and a PCDH19 Alliance grant to P.T.
PY - 2020/12
Y1 - 2020/12
N2 - PCDH19 Clustering Epilepsy (CE) is an intriguing early-onset seizure, autism and neurocognitive disorder with unique inheritance. The causative gene, PCDH19, is on the X-chromosome and encodes a cell–cell adhesion protein with restricted expression during brain development. Unlike other X-linked disorders, PCDH19-CE manifests in heterozygous females. Strikingly, hemizygous males are not affected. However, males with postzygotic somatic mutation in PCDH19 are affected and clinically similar to the affected females. PCDH19-CE is a disorder of cellular mosaicism. The coexistence of two different, but otherwise ‘normal’ cells in a PCDH19-CE individual, that is the wild type and the variant PCDH19 cells, has been proposed as the driving force of the disorder. This ‘cellular interference’ hypothesis could and has now been tested using sophisticated mouse models.
AB - PCDH19 Clustering Epilepsy (CE) is an intriguing early-onset seizure, autism and neurocognitive disorder with unique inheritance. The causative gene, PCDH19, is on the X-chromosome and encodes a cell–cell adhesion protein with restricted expression during brain development. Unlike other X-linked disorders, PCDH19-CE manifests in heterozygous females. Strikingly, hemizygous males are not affected. However, males with postzygotic somatic mutation in PCDH19 are affected and clinically similar to the affected females. PCDH19-CE is a disorder of cellular mosaicism. The coexistence of two different, but otherwise ‘normal’ cells in a PCDH19-CE individual, that is the wild type and the variant PCDH19 cells, has been proposed as the driving force of the disorder. This ‘cellular interference’ hypothesis could and has now been tested using sophisticated mouse models.
UR - http://www.scopus.com/inward/record.url?scp=85088625867&partnerID=8YFLogxK
U2 - 10.1016/j.gde.2020.06.012
DO - 10.1016/j.gde.2020.06.012
M3 - Review article
C2 - 32726744
AN - SCOPUS:85088625867
SN - 0959-437X
VL - 65
SP - 169
EP - 175
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
ER -