PTPN4 germline variants result in aberrant neurodevelopment and growth

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish
Article number100033
JournalHuman Genetics and Genomics Advances
Issue number3
StatePublished - 8 Jul 2021
Externally publishedYes


  • Developmental Delay
  • Intellectual Disability
  • Macrocephaly
  • Neurodevelopment
  • PTPN4
  • Protein tyrosine phosphatase
  • Somatic growth anomaly


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