PTBP1 variants displaying altered nucleocytoplasmic distribution are responsible for a neurodevelopmental disorder with skeletal dysplasia.

ABSTRACT: Polypyrimidine tract-binding protein 1 (PTBP1) is a heterogeneous nuclear ribonucleoprotein primarily known for its alternative splicing activity. It shuttles between the nucleus and cytoplasm via partially overlapping N-terminal nuclear localization (NLS) and export (NES) signals. Despite its fundamental role in cell growth and differentiation, its involvement in human disease remains poorly understood. We identified 27 individuals from 25 families harboring de novo or inherited pathogenic variants - predominantly start-loss (89%) and, to a lesser extent, missense (11%) - affecting NES/NLS motifs. Affected individuals presented with a syndromic neurodevelopmental disorder and variable skeletal dysplasia with disproportionate short stature with short limbs. Intellectual functioning ranged

SUBMITTER: Masson A 

PROVIDER: S-EPMC12618068 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature