Mutations of PTPN23 in developmental and epileptic encephalopathy
Hashem, Mais Omar
Arold, Stefan T.
Alkuraya, Fowzan S.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
MetadataShow full item record
AbstractDevelopmental 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.
CitationSowada N, Hashem MO, Yilmaz R, Hamad M, Kakar N, et al. (2017) Mutations of PTPN23 in developmental and epileptic encephalopathy. Human Genetics 136: 1455–1461. Available: http://dx.doi.org/10.1007/s00439-017-1850-3.
SponsorsWe 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.
- Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay.
- Authors: Saitsu H, Fukai R, Ben-Zeev B, Sakai Y, Mimaki M, Okamoto N, Suzuki Y, Monden Y, Saito H, Tziperman B, Torio M, Akamine S, Takahashi N, Osaka H, Yamagata T, Nakamura K, Tsurusaki Y, Nakashima M, Miyake N, Shiina M, Ogata K, Matsumoto N
- Issue date: 2016 Jan
- De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy.
- Authors: Sakai Y, Fukai R, Matsushita Y, Miyake N, Saitsu H, Akamine S, Torio M, Sasazuki M, Ishizaki Y, Sanefuji M, Torisu H, Shaw CA, Matsumoto N, Hara T
- Issue date: 2016 Jul
- De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures.
- Authors: Myers CT, Stong N, Mountier EI, Helbig KL, Freytag S, Sullivan JE, Ben Zeev B, Nissenkorn A, Tzadok M, Heimer G, Shinde DN, Rezazadeh A, Regan BM, Oliver KL, Ernst ME, Lippa NC, Mulhern MS, Ren Z, Poduri A, Andrade DM, Bird LM, Bahlo M, Berkovic SF, Lowenstein DH, Scheffer IE, Sadleir LG, Goldstein DB, Mefford HC, Heinzen EL
- Issue date: 2017 Oct 5
- Early epileptic encephalopathies associated with STXBP1 mutations: Could we better delineate the phenotype?
- Authors: Barcia G, Chemaly N, Gobin S, Milh M, Van Bogaert P, Barnerias C, Kaminska A, Dulac O, Desguerre I, Cormier V, Boddaert N, Nabbout R
- Issue date: 2014 Jan
- Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy.
- Authors: Assoum M, Philippe C, Isidor B, Perrin L, Makrythanasis P, Sondheimer N, Paris C, Douglas J, Lesca G, Antonarakis S, Hamamy H, Jouan T, Duffourd Y, Auvin S, Saunier A, Begtrup A, Nowak C, Chatron N, Ville D, Mireskandari K, Milani P, Jonveaux P, Lemeur G, Milh M, Amamoto M, Kato M, Nakashima M, Miyake N, Matsumoto N, Masri A, Thauvin-Robinet C, Rivière JB, Faivre L, Thevenon J
- Issue date: 2016 Dec 1