Mutations of PTPN23 in developmental and epileptic encephalopathy

Human Genetics
Nadine SowadaGuntram Borck

Abstract

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.

References

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Citations

Feb 23, 2020·Journal of Cell Science·Marta I BudzinskaGiampietro Schiavo
May 21, 2020·Disease Models & Mechanisms·Rebecca YarwoodMartin Lowe
Aug 12, 2019·Epilepsy & Behavior : E&B·Pedro H M MagalhãesIscia Lopes-Cendes
Jun 24, 2021·The Journal of Cell Biology·Chun-Che TsengDavid J Katzmann

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