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.
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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.
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On behalf of all authors, the corresponding author states that there is no conflict of interest.
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Sowada, N., Hashem, M.O., Yilmaz, R. et al. Mutations of PTPN23 in developmental and epileptic encephalopathy. Hum Genet 136, 1455–1461 (2017). https://doi.org/10.1007/s00439-017-1850-3