TY - JOUR
T1 - Mutations of PTPN23 in developmental and epileptic encephalopathy
AU - Sowada, Nadine
AU - Hashem, Mais Omar
AU - Yilmaz, Rüstem
AU - Hamad, Muddathir
AU - Kakar, Naseebullah
AU - Thiele, Holger
AU - Arold, Stefan T.
AU - Bode, Harald
AU - Alkuraya, Fowzan S.
AU - Borck, Guntram
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank the families for their participation in this research project. The research by STA reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST). The exome analysis was performed on CHEOPS, a high performance computer cluster of the regional data center of the University of Cologne (RRZK), funded by the Deutsche Forschungsgemeinschaft (DFG). We acknowledge the support of the Saudi Human Genome Program.
PY - 2017/10/31
Y1 - 2017/10/31
N2 - Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of neurodevelopmental disorders with poor prognosis. Recent discoveries have greatly expanded the repertoire of genes that are mutated in epileptic encephalopathies and DEE, often in a de novo fashion, but in many patients, the disease remains molecularly uncharacterized. Here, we describe a new form of DEE in patients with likely deleterious biallelic variants in PTPN23. The phenotype is characterized by early onset drug-resistant epilepsy, severe and global developmental delay, microcephaly, and sometimes premature death. PTPN23 encodes a tyrosine phosphatase with strong brain expression, and its knockout in mouse is embryonically lethal. Structural modeling supports a deleterious effect of the identified alleles. Our data suggest that PTPN23 mutations cause a rare severe form of autosomal-recessive DEE in humans, a finding that requires confirmation.
AB - Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of neurodevelopmental disorders with poor prognosis. Recent discoveries have greatly expanded the repertoire of genes that are mutated in epileptic encephalopathies and DEE, often in a de novo fashion, but in many patients, the disease remains molecularly uncharacterized. Here, we describe a new form of DEE in patients with likely deleterious biallelic variants in PTPN23. The phenotype is characterized by early onset drug-resistant epilepsy, severe and global developmental delay, microcephaly, and sometimes premature death. PTPN23 encodes a tyrosine phosphatase with strong brain expression, and its knockout in mouse is embryonically lethal. Structural modeling supports a deleterious effect of the identified alleles. Our data suggest that PTPN23 mutations cause a rare severe form of autosomal-recessive DEE in humans, a finding that requires confirmation.
UR - http://hdl.handle.net/10754/626581
UR - http://link.springer.com/article/10.1007/s00439-017-1850-3
UR - http://www.scopus.com/inward/record.url?scp=85032659022&partnerID=8YFLogxK
U2 - 10.1007/s00439-017-1850-3
DO - 10.1007/s00439-017-1850-3
M3 - Article
C2 - 29090338
AN - SCOPUS:85032659022
VL - 136
SP - 1455
EP - 1461
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 11-12
ER -