The First Case Report of a Homozygous Consensus Acceptor Splice Variant in the NUP214 Gene Associated With Fetal...

The NUP214 gene encodes a nuclear pore complex protein (nucleoporin, 214 kilodaltons) which plays a critical role in messenger RNA export to the cytoplasm and import of substrates from the cytoplasm. Biallelic mutations in the NUP214 gene have been associated with susceptibility to acute infection-induced encephalopathy type 9 (ILAE9) (Online Mendelian Inheritance in Man (OMIM), 114350), an autosomal recessive disorder. Herein, we describe for the first time, a fetus with hydrops and arthrogryposis multiplex with a homozygous novel consensus splice site variant in the NUP214 gene, chr9:g.131127522A>G or c.46-2A>G (transcript ID NM_005085.4). Parents were heterozygous for the same variant. Mutations in either of 83 genes have been previously published to cause fetal arthrogryposis multiplex but mutations in NUP214 have not been previously reported as per our search in the available medical literature (PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online) and Google Scholar). STRING (Search Tool for Retrieval of Interacting Genes/Proteins) analysis showed close interactions between NUP214 and the other proteins GLE1, NUP88, NEK9, and THOC2. Thus, this case report expands the phenotype of NUP214 gene-related human disease.