Why are we an umbrella organization?

The hnRNPs are as much of a community in the cell as we are at the HNRNP Family Foundation.

The HNRNPs are genes encoding for the heterogenous nuclear ribonucleoproteins (also called hnRNPs when referring to the proteins). The hnRNPs are a large family of ~30 RNA binding proteins. These proteins are incredibly important in the cell and contribute to many aspects of RNA processing of many genes.

This includes:

alternative splicing (deciding which version of a gene is expressed)
mRNA stabilization (making sure the expressed genes don’t get degraded)
regulation of transcription (deciding which genes get expressed where)
and regulation of transcription (helping decide which mRNAs are made into proteins)

We also know that the hnRNPs look similar on a molecular level. Additionally, the hnRNPs can work together and compensate for each other.

The importance of the HNRNP genes

hnRNPs have been of great interest in the medical world for a long time due to their involvement in cancers and neurodegenerative disorders, which is often through changes in expression of the hnRNPs themselves. In contrast, the HNRNP-RNDDs are caused by variants within the genes.

RNA binding proteins in general have a significant role in neurodevelopment.

Each hnRNP has a unique role, although they often overlap. From the time a gene is made into RNA to the point its made into protein, an hnRNP is involved.

Individual HNRNP-RNDDs

The HNRNP-RNDDs are related but distinct disorders. We have color coded them by which are more related to each other.

Here's what we know is different

HNRNPC-RNDD

HNRNPC-RNDD is one of the newest HNRNP-RNDDs described.

Most individuals with HNRNPC-RNDD have a happy demeanor

HNRNPD-RNDD

HNRNPD-RNDD has only been described in one paper.

Speech is particularly affected
Behavioral differences such as autism spectrum disorder are common
Differences in movement (ataxia, poor coordination, dystonia) have been observed

HNRNPG-RNDD

hnRNPG variants result in Shashi-related intellectual disability, which has only been described in a few families. The disorder is X-linked and only affects males (who have one copy of the X chromosome).

Many have short stature
Hearing is often affected
There are shared differences in facial features

HNRNPH1-RNDD

HNRNPH1-RNDD has multiple papers published on it.

Growth delay is common
Speech is particularly affected
MRI abnormalities are common
Vision and eye issues are common
Differences in facial features are common

HNRNPH2-RNDD

HNRNPH2-RNDD is also known as Bain-type intellectual disability. Mostly girls are affected, but a small number of boys have been reported.

Many individuals have genetic variants that impact the same part of the protein
Growth delay is observed in many individuals
Speech and motor skills are significantly affected
Behavioral differences are common, including autism spectrum disorder, anxiety, and hyperacusis
Vision issues are common
There are consistent facial features

HNRNPK-RNDD

Variants in HNRNPK cause Au-Kline Syndrome.

There are distinct facial features observed in many individuals with Au-Kline Syndrome.
Skeletal differences, including scoliosis, are common
~20% of cases have craniosynostosis
Congenital hip dysplasia is common
Many individuals have heart issues

HNRNPR-RNDD

HNRNPR-RNDD has been in two publications.

Many individuals have growth delay
Many have behavioral differences, such as autism spectrum disorder and attention deficit hyperactivity disorder
Skeletal differences have been reported, such as scoliosis or hand and feet differences such as clinodactyly
There are not specific facial features, but many individual have differences in ear structure, and microcephaly is common
Cardiac issues are reported in half of cases

HNRNPQ-RNDD

HNRNPQ/SYNCRIP-RNDD has been in multiple publications.

Most individuals have speech and/or language delay, and many are nonverbal
Behavioral differences such as autism spectrum disorder are common

HNRNPU-RNDD

HNRNPU-RNDD is fairly well characterized, with several publications.

Seizures are reported in almost all cases
Speech and language delay is common

HNRNPUL2-RNDD

HNRNPUL2-RNDD has only one publication.

Growth delay is common
Both speech and motor skills are delayed
Behavioral differences such as autism spectrum disorder and ADHD are common