PTPN4 germline variants result in aberrant neurodevelopment and growth
Summary: 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 sequencin...
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doaj-5c1338c329174b3086e0712d587253962021-07-09T04:45:09ZengElsevierHGG Advances2666-24772021-07-0123100033PTPN4 germline variants result in aberrant neurodevelopment and growthJoanna J. Chmielewska0Deepika Burkardt1Jorge Luis Granadillo2Rachel Slaugh3Shamile Morgan4Joshua Rotenberg5Boris Keren6Cyril Mignot7Luis Escobar8Peter Turnpenny9Melissa Zuteck10Laurie H. Seaver11Rafal Ploski12Magdalena Dziembowska13Anthony Wynshaw-Boris14Abidemi Adegbola15Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland; Laboratory of Molecular Basis of Synaptic Plasticity, Centre of New Technologies, University of Warsaw, Warsaw, PolandCenter for Human Genetics and Department of Genetics and Genome Sciences, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, OH, USADivision of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USADivision of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USAHouston Specialty Clinic, Houston, TX, USAHouston Specialty Clinic, Houston, TX, USADépartement de Génétique, APHP, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceDépartement de Génétique, APHP, Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Centre de Référence Déficiences Intellectuelles de Causes Rares, Paris, FranceMedical Genetics and Neurodevelopmental Center, Peyton Manning Children’s Hospital, Indianapolis, IN, USAUniversity of Exeter Medical School and Royal Devon and Exeter NHS Foundation Trust, Exeter, UKMedical Genetics and Genomics, Spectrum Health/Helen Devos Children’s Hospital, Grand Rapids, MI, USAMedical Genetics and Genomics, Spectrum Health/Helen Devos Children’s Hospital, Grand Rapids, MI, USA; Department of Pediatrics and Human Development, Michigan State College of Human Medicine, Grand Rapids, MI, USADepartment of Medical Genetics, Warsaw Medical University, Warsaw, PolandLaboratory of Molecular Basis of Synaptic Plasticity, Centre of New Technologies, University of Warsaw, Warsaw, PolandCenter for Human Genetics and Department of Genetics and Genome Sciences, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, OH, USACenter for Human Genetics and Department of Genetics and Genome Sciences, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, OH, USA; Department of Psychiatry, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, OH, USA; Corresponding authorSummary: 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 PTPN4 in six unrelated individuals with varying degrees of intellectual disability or developmental delay. The variants occurred de novo 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. PTPN4 is a widely expressed protein tyrosine phosphatase that regulates neuronal cell homeostasis by protecting neurons against apoptosis. We suggest that pathogenic variants in PTPN4 confer risk for growth and cognitive abnormalities in humans.http://www.sciencedirect.com/science/article/pii/S2666247721000142NeurodevelopmentDevelopmental DelayIntellectual DisabilityMacrocephalySomatic growth anomalyPTPN4 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joanna J. Chmielewska Deepika Burkardt Jorge Luis Granadillo Rachel Slaugh Shamile Morgan Joshua Rotenberg Boris Keren Cyril Mignot Luis Escobar Peter Turnpenny Melissa Zuteck Laurie H. Seaver Rafal Ploski Magdalena Dziembowska Anthony Wynshaw-Boris Abidemi Adegbola |
spellingShingle |
Joanna J. Chmielewska Deepika Burkardt Jorge Luis Granadillo Rachel Slaugh Shamile Morgan Joshua Rotenberg Boris Keren Cyril Mignot Luis Escobar Peter Turnpenny Melissa Zuteck Laurie H. Seaver Rafal Ploski Magdalena Dziembowska Anthony Wynshaw-Boris Abidemi Adegbola PTPN4 germline variants result in aberrant neurodevelopment and growth HGG Advances Neurodevelopment Developmental Delay Intellectual Disability Macrocephaly Somatic growth anomaly PTPN4 |
author_facet |
Joanna J. Chmielewska Deepika Burkardt Jorge Luis Granadillo Rachel Slaugh Shamile Morgan Joshua Rotenberg Boris Keren Cyril Mignot Luis Escobar Peter Turnpenny Melissa Zuteck Laurie H. Seaver Rafal Ploski Magdalena Dziembowska Anthony Wynshaw-Boris Abidemi Adegbola |
author_sort |
Joanna J. Chmielewska |
title |
PTPN4 germline variants result in aberrant neurodevelopment and growth |
title_short |
PTPN4 germline variants result in aberrant neurodevelopment and growth |
title_full |
PTPN4 germline variants result in aberrant neurodevelopment and growth |
title_fullStr |
PTPN4 germline variants result in aberrant neurodevelopment and growth |
title_full_unstemmed |
PTPN4 germline variants result in aberrant neurodevelopment and growth |
title_sort |
ptpn4 germline variants result in aberrant neurodevelopment and growth |
publisher |
Elsevier |
series |
HGG Advances |
issn |
2666-2477 |
publishDate |
2021-07-01 |
description |
Summary: 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 PTPN4 in six unrelated individuals with varying degrees of intellectual disability or developmental delay. The variants occurred de novo 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. PTPN4 is a widely expressed protein tyrosine phosphatase that regulates neuronal cell homeostasis by protecting neurons against apoptosis. We suggest that pathogenic variants in PTPN4 confer risk for growth and cognitive abnormalities in humans. |
topic |
Neurodevelopment Developmental Delay Intellectual Disability Macrocephaly Somatic growth anomaly PTPN4 |
url |
http://www.sciencedirect.com/science/article/pii/S2666247721000142 |
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