HNRNPU-RNDD is caused by changes, or variation, of the HNRNPU gene. HNRNPU encodes for an RNA binding protein called heterogeneous nuclear ribonucleoprotein U (hnRNPU). hnRNPU and other hnRNPs are very important in RNA processing in the cell, which can affect many different body systems.
Most variants that cause HNRNPU-RNDD occur de novo, meaning that they are not present in either parent. If a parent does not carry the variant, it is very unlikely that future children would be affected. These are often loss-of-function variants, resulting in haploinsufficiency –only half of the expected protein amount is made in the cells. This disrupts how the cell works. Missense variants (changing one amino acid to another amino acid) have also been reported.
HNRNPU-RNDD can also be the result of a larger chromosomal deletion, removing part of chromosome 1 (1q43q44). These deletions may include only HNRNPU or HNRNPU and other genes, which can impact the clinical features. The larger deletions are referred to as 1q43q44 deletion syndrome, which shares many characteristics with HNRNPU-RNDD.
HNRNPU