Biallelic variants, which lead to loss of function of NEPRO, have been identified as the cause for NEPRO-related skeletal dysplasia. All the families described till date are consanguineous and have homozygous variants. Heterozygous carriers of the variants do not have any phenotypic features.
NEPRO encodes for the NEPRO (Nucleolus and neural progenitor protein), which consists of 567 amino acids. The protein is present in the nucleolus. The function of NEPRO has not completely been unravelled. Its function has been mainly investigated in neural progenitor cells and in embryogenesis. Knockout studies in mice embryo demonstrated abnormal number of nucleolus precursor bodies and nucleoli. NEPRO interacts with multiple subunits of RNase P/MRP ribonucleoprotein complex, like RMRP and POP1. More functional studies are required to prove the interaction and effect of NEPRO on RMRP endoribonuclease complex.
The two unrelated Saudi Arabian families had the biallelic missense variant c.280C>T in NEPRO. The affected individual from the Indian family had a novel homozygous missense variant, c.435G>C, p.(Leu145Phe) in exon 4 of NEPRO. NEPRO is located on chromosome 3q13.2 and was previously named as C3orf17. It has 9 coding exons. Variants may be identified by sequencing of all the coding exons.
NEPRO