Background: Congenital aniridia is a severe ocular abnormality characterized by incomplete formation of the iris and many other ocular complications. Most cases are caused by the paired box 6 (PAX6) gene mutations generating premature termination codons (PTCs).Methods: Ophthalmic examination was performed on a Chinese pedigree with congenital aniridia. The mutation was identified by targeted next‐generation sequencing. Nonsense suppression therapy was applied on patient‐derived lymphocytes. The PAX6 expression was assayed by real‐time polymerase chain reaction and Western blot.Results: Complete aniridia was complicated with horizontal nystagmus, contract, foveal hypoplasia, and microphthalmia. A novel heterozygous c.702_703delinsAT (p.Tyr234*) mutation was found in exon 9 of PAX6, generating a PTC at the homeodomain. There were about 50% reductions of both full‐length PAX6 protein and PAX6 mRNA in patient‐derived lymphocytes, indicating haploinsufficiency due to nonsense‐mediated mRNA decay. Ataluren (PTC124) and geneticin (G418) could induce about 30%–40% translational readthrough. Nonsense suppression therapy restored PAX6 protein to about 65%–70% of unaffected family controls.Conclusion: Our data expanded the genetic and phenotypic variations of congenital aniridia, and showed the therapeutic effect of nonsense suppression on this disease using patient‐derived cells.

Paclitaxel (PTX)-based chemotherapy is a standard treatment for human lung adenocarcinoma, but treatment often fails since resistance develops. Recent studies have described the activity of long non-coding RNAs (lncRNAs) in many biological processes and human diseases. Chemotherapy resistance is one of these areas, but the role of lncRNAs in paclitaxel resistance of human lung adenocarcinoma cells has not been reported. A paclitaxel resistance model was established using A549 human lung adenocarcinoma cells. lncRNAs and mRNAs were profiled in parental A549 and paclitaxel-resistant A549/PTX cells by microarray analysis. Real-time quantitative PCR (RT-qPCR) was used to validate the results of the microarray. Chromosomal distribution patterns of differentially expressed lncRNAs and mRNAs were assessed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using gene set enrichment. We screened 1,154 lncRNAs and 1,733 mRNAs that had a >3-fold difference in expression in A549/PTX cells compared with A549 cells, most of which were downregulated. Nine lncRNAs and six mRNAs were randomly selected and validated by RT-qPCR. Most aberrantly expressed lncRNAs and mRNAs were located on chromosomes 1, 2, 6, 12 and 17, particularly on chromosome 1. Bioinformatics, GO and KEGG pathway analyses, revealed that some differentially expressed genes regulated classical functions and pathways such as cytosol components, protein binding, gene expression and metabolic pathways. Differential expression of lncRNAs and mRNAs in A549/PTX and A549 cells indicates that various lncRNAs may be useful diagnostic or prognostic markers of resistance to treatment, or future targets for paclitaxel-based chemotherapy, providing a novel rationale for clinical treatment.

Background: Multiple acyl-coenzyme A (CoA) dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from mutations in the ETFDH gene. It is characterized by a wide spectrum of clinical symptoms, of which polycystic kidney disease is a specific phenotype of early-onset MADD. This study aims to broaden the genetic mutation spectrum of ETFDH gene. And we clarify the pathogenic mechanism of polycystic kidney caused by the loss of function of the ETFDH gene through in vitro experiments. Results: Compound heterozygous variants in ETFDH (NM_004453: c.487 + 2 T > A, c.1395 T > G and c.1773–1774 del AT(in cis with c.1395 T > G) were identifed via trio-Whole Exome Sequencing (trio-WES) and confirmed pathogenic through Minigene Splice Assay and RT-PCR. This study, for the first time, demonstrated through both in vivo and in vitro experiments that c.487 + 2 T > A mutation lead to mRNA degradation through nonsense-mediated decay (NMD). Further cell experiments showed that downregulation of ETFDH gene led to lipid accumulation, enhanced oxidative stress, and upregulation of ZNF267 expression. Conclusions: This study clarify the pathogenicity of c.487 + 2 T > A and c.1395 T > G mutations, aiding in the diagnosis and genetic counseling of ETFDH in clinical practice. The significance of this study is to reveal that ETFDH gene may be a key regulatory gene in the development of polycystic kidney.

Background: Non-invasive prenatal testing (NIPT) has become the widely adopted prenatal testing for screening the common aneuploidy of pregnant woman and even expented to detecting copy number variations (CNVs) and Monogenic disease. In recent 10 years, NIPT has become an increasingly important scholarly focus. However, date on long-term bibliometric studies on NIPT has not been reported. Objective: The purpose of this study was to map publications trends and to explore the knowledge structure on NIPT. Methods: Publications were collected from database PubMed in the past 10 years. A bibliometric analysis based on PubMed was conducted to investigate the publication trends and the knowledge structure. Co-word blustering analysis and strategic diagram of highly frequent major MeSH terms were utilized to detect the hot spots in this field. Results: A total of 2160 articles about NIPT were retrieved according to our search strategy in this study. Article was the main document type. The 10 most active journals published 29.3% (633/2160) of the publications in this area. By analyzing and summarizing the highly frequent major MeSH, 7 research hot spots were founded.Conclusion: Our data indicated that NIPT mainly focuses on the 7 major research hot spots, and strategic diagram provides some hints for the future research trend of NIPT.