The First Case Report of a Homozygous Consensus Acceptor Splice Variant in the NUP214 Gene Associated With Fetal Hydrops and Arthrogryposis Multiplex

The <i>NUP214</i> 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 <i>NUP214</i> 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 <i>NUP214</i> 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 <i>NUP214</i> and the other proteins GLE1, NUP88, NEK9, and THOC2. Thus, this case report expands the phenotype of <i>NUP214</i> gene-related human disease.