biostudies-literatureChmielewska JJNational Center for Advancing Translational SciencesCenter for Advanced Systems and Engineering, Syracuse UniversityNarodowe Centrum NaukiNIMH NIH HHSNational Institutes of HealthWellcome Trust100033https://www.ebi.ac.uk/biostudies/studies/S-EPMC8439436biostudies-literatureUnknown2(3)Protein-tyrosine phosphatases (PTPs) are pleomorphic regulators of eukaryotic cellular responses to extracellular signals that function by modulating the phosphotyrosine of specific proteins. A handful of PTPs have been implicated in germline and somatic human disease. Using exome sequencing, we identified missense and truncating variants in <i>PTPN4</i> in six unrelated individuals with varying degrees of intellectual disability or developmental delay. The variants occurred <i>de novo</i> in all five subjects in whom segregation analysis was possible. Recurring features include postnatal growth deficiency or excess, seizures, and, less commonly, structural CNS, heart, or skeletal anomalies. <i>PTPN4</i> is a widely expressed protein tyrosine phosphatase that regulates neuronal cell homeosHGG advances<i>PTPN4</i> germline variants result in aberrant neurodevelopment and growth.PMC8439436R01MH113106R01 MH1131062014/14/E/NZ3/00375Keren BBurkardt DMignot CWynshaw-Boris AChmielewska JJSlaugh RSeaver LHGranadillo JLAdegbola AZuteck MMorgan SDziembowska MEscobar LTurnpenny PRotenberg JPloski Rfalse<i>PTPN4</i> germline variants result in aberrant neurodevelopment and growth.Protein-tyrosine phosphatases (PTPs) are pleomorphic regulators of eukaryotic cellular responses to extracellular signals that function by modulating the phosphotyrosine of specific proteins. A handful of PTPs have been implicated in germline and somatic human disease. Using exome sequencing, we identified missense and truncating variants in <i>PTPN4</i> in six unrelated individuals with varying degrees of intellectual disability or developmental delay. The variants occurred <i>de novo</i> in all five subjects in whom segregation analysis was possible. Recurring features include postnatal growth deficiency or excess, seizures, and, less commonly, structural CNS, heart, or skeletal anomalies. <i>PTPN4</i> is a widely expressed protein tyrosine phosphatase that regulates neuronal cell homeos2021-01-01T00:00:00Z2021 Jul2026-06-12T09:13:12.34Z2022-02-11T16:14:22.017ZS-EPMC84394363452796310.1016/j.xhgg.2021.100033