PTBP1 (HNRNPI)-Related Neurodevelopmental Disorder
PTBP-related neurodevelopmental disorder (also called PTBP1-RNDD) is a rare genetic condition caused by changes in the PTBP1 gene, which plays an important role in how the brain develops and communicates. The condition can vary widely from person to person, with some individuals mildly affected while others experience more significant challenges.
PTBP1 variants displaying altered nucleocytoplasmic distribution are responsible for a neurodevelopmental disorder with skeletal dysplasia
(2025)
View PDFThe Gene
PTBP1 (polypyrimidine tract-binding protein 1) encodes for heterogeneous nuclear ribonuclear protein I (hnRNPI). Individuals with PTBP1-RNDD have variants that result in the protein being improperly made.
hnRNPI helps the body process RNA — the instructions cells use to make proteins and keeps the genome stable. Specifically, hnRNPI plays roles in:
The gene is expressed all over the body (ubiquitously), with especially high expression in the heart and brain.
Why It Matters for the Brain
hnRNPI helps control a process called alternative splicing — a mechanism cells use to "edit" RNA before making proteins. Think of this as cutting and assembling sentence fragments into different final messages. When hnRNPI does not work correctly due to too low of levels or other changes to the protein, this editing process can become inconsistent. Research found that the genes most affected by these disruptions are genes already known to be associated with intellectual disability and brain development. In other words: hnRNPI doesn't cause problems on its own — but without enough of it, many other important brain-development genes don't function properly.
Most hnRNPI variants occur de novo, meaning they are random and not from either parent, although inherited variants from affected parents have been reported.
Variant types observed:
- Start-loss variants, which remove the early part of the protein
- Missense variants altering single amino acids
Disrupted RNA Splicing
hnRNPI helps control alternative splicing — the process of "editing" RNA before making proteins. When hnRNPI doesn't function properly, this editing process becomes inconsistent, affecting the production of many proteins important for brain development.
Impact on Brain Development Genes
Research has shown that the genes most affected by hnRNPI disruption are those already known to be associated with intellectual disability and brain development. hnRNPI acts as a regulator that, when absent or dysfunctional, prevents many other critical genes from functioning properly.
Neurodevelopmental Differences
Individuals with PTBP1-RNDD may experience neurodevelopmental differences. The severity can vary significantly from person to person.
Skeletal Dysplasia
Skeletal differences have been observed in individuals with PTBP1-RNDD, as noted in the initial publication describing the condition.
Receiving a PTBP1-RNDD diagnosis can feel overwhelming, but you are not alone. While this is an extremely rare condition that was only first described in 2025, our community is here to support you. Every individual with PTBP1-RNDD is unique, and the clinical features described here represent what has been observed across all known cases—your child may experience some, none, or different combinations of these features.
- PTBP1-RNDD was only recently discovered in 2025, meaning research is actively ongoing.
- The underlying biology is becoming clearer, which is the foundation for future treatments.
- Early support and therapies (speech, motor, behavioral, and educational strategies) can make a meaningful difference.
- Connect with other families through our Facebook groups and the HNRNP Family Foundation community.
Want to learn more about other HNRNP-RNDDs?
Explore our comprehensive resources on all HNRNP-Related Neurodevelopmental Disorders.
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