Edition of 08 July 2025

A new study published in The Lancet Neurology described heterozygous loss-of-function variants of PTPN1, encoding a protein tyrosine phosphatase which serves as a key regulator of intracellular signalling in multiple types of cells, including in the immune system. The variants were found among 12 individuals from 11 families who suffered from subacute onset loss of motor and language skills following initially normal development, spastic dystonia, bulbar involvement, preserved head circumference, and an absence of seizures. Various analyses confirmed the role of PTPN1 in type 1 IFN signalling and identified PTPN1 deficiency, an autosomal dominant disorder, as a novel type 1 interferonopathy leading to an autoinflammatory encephalopathy.