All HNRNPC-RNDD individuals have developmental delay/intellectual disability to date. This ranges from mild to moderate.
All HNRNPC-RNDD individuals have speech delay or problems. Some individuals are nonverbal while some are delayed until 2-3 years old. Multiple people have articulation issues.
Most individuals with HNRNPC-RNDD have motor delay. One individual who has a large exon 1-3 deletion did not have gross motor delay, but other individuals had delayed walking, with first steps being up to 2.5 years old. All individuals have delays in fine motor skills.
The Genetics of HNRNPC-RNDD
Above are the two isoforms of hnRNPC at the protein level. Isoform 1 is at the top and isoform 2 is at the bottom. RRM: RNA Recognition Motif (important for RNA binding), bZLM (basic region zipper-like motif, CLZ: leucine-zipper like oligomerization domain, CTD: C-terminal domain. Variants are shown for each isoform. Also shown is the exact DNA change for the recurrent C-terminal deletions.
HNRNPC has two isoforms, or versions. These are called isoform 1 (NM_004500.4, top) and isoform 2 (NM_031314.3, bottom). Isoform 1 is expressed more than isoform 2.
Multiple variant types have been observed. These include:
Large deletions of multiple exons. These likely result in loss of function. (light blue in diagram)
Missense variants. These may disrupt how the hnRNPC protein works. (black in diagram)
Frameshift variants. These likely result in loss of function. (yellow in diagram)
Small deletions of amino acids 284-292, resulting in a truncated protein. This exact variant has been seen in multiple patients.