Description

Transportin-2 (TNPO2) encodes a member of the importin-β family of nuclear transport receptors, which mediate the selective transport of proteins containing nuclear localization signals from the cytoplasm into the nucleus. Nucleocytoplasmic transport is essential for numerous cellular processes, including gene regulation, RNA metabolism, cell differentiation, and neuronal development. Proper nuclear import is particularly critical during embryonic brain development, where tightly regulated trafficking of transcription factors and RNA-binding proteins is required for normal neurodevelopment.

Pathogenic germline variants in TNPO2 have recently been identified as the cause of a rare neurodevelopmental disorder. Reported individuals commonly present with global developmental delay, intellectual disability, hypotonia, delayed motor and language development, epilepsy in a subset of patients, and variable behavioral abnormalities, including features of autism spectrum disorder and schizophrenia. Additional manifestations, such as movement disorders, feeding difficulties, and dysmorphic features, have been described in some individuals. However, the phenotypic spectrum, disease mechanisms, and long-term clinical course remain incompletely understood due to the limited number of reported cases.

As additional patients are identified through genome and exome sequencing, the spectrum of TNPO2-associated disorders is expected to expand. Systematic collection of standardized clinical and molecular data is therefore essential to improve understanding of disease pathogenesis, define genotype-phenotype correlations, and establish evidence-based recommendations for clinical care.

Purpose of the Registry The TNPO2- Registry is an international, multicenter observational registry designed to collect comprehensive clinical, genetic, neurodevelopmental, and longitudinal data from individuals with pathogenic or likely pathogenic variants in the TNPO2 gene, as well as selected individuals with variants of uncertain significance supported by compatible clinical phenotypes.

The registry aims to create a centralized resource that facilitates collaboration among clinicians, researchers, and patient organizations while advancing knowledge of the natural history, clinical variability, and molecular basis of TNPO2-associated disorders.

Aditionally this study aims to characterize the variants and identify the underlying pathomachanism that is causative for the disorder using PBMCs from patients. These findings aim to test multiple FDA approved drugs to identify novel treatment options.