A novel NHS mutation in a Chinese family with Nance­Horan Syndrome.

Nance­Horan syndrome (NHS) is a rare X­linked disorder with various clinical manifestations. The present study aimed to identify the pathogenic mutation causing NHS in a three­generation Chinese family with 4 individuals presenting primarily with congenital cataracts. The genomic DNA of 5 individuals was collected, and family history and clinical information were recorded. Whole exome sequencing was performed on the proband, and candidate mutations were filtered by a series of screening processes and validated by Sanger sequencing. The identified pathogenic mutation was confirmed by co­segregation analysis. Finally, a novel frameshift mutation (NM_001291867.1: c.302dupA; p.Ala102fs) was identified in the NHS actin remodeling regulator (NHS) gene, which co­segregated with congenital cataracts in this family. Carrier females exhibited similar but milder clinical symptoms compared with the affected male. These clinical symptoms were consistent with the phenotypic features of the NHS­associated disease, NHS. In summary, the present study identified a novel NHS mutation in a Chinese family with atypical NHS; the results broaden the known pathogenic mutation spectrum of NHS and will aid in the genetic counseling of patients with NHS. The data from the present study also suggest that genetic analysis may be required for the diagnosis of this disease.

Novel missense mutation in PTPN22 in a Chinese pedigree with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis is a complex autoimmune thyroid disease, the onset of which is associated with environmental exposures and specific susceptibility genes. Its incidence in females is higher than its incidence in males. Thus far, although some susceptibility loci have been elaborated, including PTPN22, FOXP3, and CD25, the aetiology and pathogenesis of Hashimoto's thyroiditis remains unclear. METHODS: Four affected members from a Chinese family with Hashimoto's thyroiditis were selected for whole-exome sequencing. Missense, nonsense, frameshift, or splicing-site variants shared by all affected members were identified after frequency filtering against public and internal exome databases. Segregation analysis was performed by Sanger sequencing among all members with available DNA. RESULTS: We identified a missense mutation in PTPN22 (NM_015967.5; c. 77A > G; p.Asn26Ser) using whole-exome sequencing. PTPN22 is a known susceptibility gene associated with increased risks of multiple autoimmune diseases. Cosegregation analysis confirmed that all patients in this family, all of whom were female, carried the mutation. All public and private databases showed that the missense mutation was extremely rare. CONCLUSIONS: We found a missense mutation in PTPN22 in a Chinese HT pedigree using whole-exome sequencing. Our study, for the first time, linked a rare variant of PTPN22 to Hashimoto's thyroiditis, providing further evidence of the disease-causing or susceptibility role of PTPN22 in autoimmune thyroid disease. Functional studies regarding the effects of this variant on thyroid autoimmunity and thyroid function are warranted.

A novel CRX frameshift mutation causing cone-rod dystrophy in a Chinese family: A case report.

BACKGROUND: Cone-rod dystrophy (CORD) is an inherited, progressive retinal disorder with genetic and phenotypic heterogeneity. Here, we aimed to identify the pathogenic mutation in affected individuals in a Chinese family with autosomal dominant cone-rod dystrophy (adCORD). METHODS: Genomic DNA and clinical examination results were collected from a Chinese family presenting with adCORD. The candidate disease-causing mutations were screened with whole-exome sequencing (WES) and bioinformatics analyses. Sanger sequencing was used for validation and cosegregation analysis. RESULTS: A novel frameshift mutation (NM_000554.4; c.538dupG:p.Val180fs) in exon 4 of the CRX gene was identified in all affected individuals in the Chinese family with adCORD. Cosegregation analysis confirmed that this mutation was cosegregated with the disease. This variant, which results in premature termination of the protein, was absent from all public variant databases or internal exome databases. CONCLUSIONS: We used whole-exome sequencing to identify a novel CRX mutation causing adCORD in a Chinese family. This study broadens the known pathogenic mutation spectrum of the CRX gene and shows the potential of WES in identifying the pathogenic mutations of CORD disease.

Piezoelectric Polyacrylonitrile Nanofiber Film-Based Dual-Function Self-Powered Flexible Sensor.

To meet the growing demands in flexible and wearable electronics, various sensors have been designed for detecting and monitoring the physical quantity changes. However, most of these sensors can only detect one certain kind of physical quantity based on a single mechanism. In this paper, we have fabricated a multifunctional sensor made from carbonized electrospun polyacrylonitrile/barium titanate (PAN-C/BTO) nanofiber film. It can detect two physical quantities (pressure and curvature), independently and simultaneously, by integrating piezoresistive, piezoelectric, and triboelectric effects. For flex sensing with the impedance change of PAN-C/BTO nanofiber films during bending, it had a sensitivity of 1.12 deg-1 from 58.9° to 120.2° and a working range of 28°-150°. For self-powered force sensing, it had a gauge factor of 1.44 V·N-1 within the range of 0.15-25 N. The sensor had a long stability over 60 000 cycles at both sensing modes. The inclusion of barium titanate nanoparticles (BTO NPs) into the nanofiber film had an over 2.4 times enhancement of sensitivity for pressure sensing because of the synergy of piezoelectric and triboelectric effects. On the basis of multifunction and modularity, a series of potential applications of the sensor were demonstrated, including sensing human's swallowing, walking gaits, finger flexure, and finger-tapping. The self-powered flexible dual-mode sensor has great application potential in human-computer interactive and smart wearable sensing systems.

Structural effect of Fe3O4 nanoparticles on peroxidase-like activity for cancer therapy.

Ferromagnetic nanoparticles (Fe3O4 NPs) have been proven to have the intrinsic peroxidase-like activity. This property has been used for analyte detection, tumor tissue visualization, and cancer therapy, etc. However, the effect of particle structure and morphology on its peroxidase-like activity has been rarely reported. In this work, we fabricated Fe3O4 nanoparticles with different structures (nanoclusters, nanoflowers, and nanodiamonds) by facilely tuning the pH values in the hydrothermal reaction. Their in vitro peroxidase-like activity was evaluated via chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) by the reduction of H2O2 to H2O. It was found the nanostructures had a great influence on their peroxidase-like activity, following the order of nanoclusters>nanoflowers>nanodiamonds. With this activity, the peroxidase-like activity of Fe3O4 NPs was used for cancer therapy with the addition of low-concentration H2O2. The cancer cell-killing activity was due to the intracellular generated reactive oxygen species (ROS) after endocytosis of Fe3O4 NPs into the Hela cells. It was interesting that the cell killing ability of these three kinds of Fe3O4 NPs was not consistent with the in vitro enzyme-like activity. It was deduced that the cell endocytosis of the nanoparticles along with their enzyme-like activity co-determined their cancer cell-killing performance.

Gelatin-Encapsulated Magnetic Nanoparticles for pH, Redox, and Enzyme Multiple Stimuli-Responsive Drug Delivery and Magnetic Resonance Imaging.

A new kind of magnetic gelatin-encapsulated nanoassembly was fabricated as a multifunctional drug delivery system (DDS) with pH, redox, and enzyme stimuli-responsive drug release for cancer theranostics. Cystamine-modified gelatin was used to encapsulate doxorubicin (Dox) as an anticancer drug and Fe3O4 as the magnetic resonance imaging (MRI) contrast agent to assembly into a nanoassembly via the formation of an oil-in-water microemulsion. Such a DDS system can provide long-term Dox release and more effective drug availability, since the acidic environment, high glutathione (GSH) and matrix metalloproteinase (MMP) level of cancer tissues. And it would beneficial for high accumulation around tumor through the enhanced penetration and retention (EPR) effect, and deeper penetration into tumor because of its enzyme-degradable and size-changeable ability. This drug delivery vehicle had good biocompatibility. It can effectively reduce the efflux of drugs when these nanoparticles were uptaken by cells. Besides, the Dox-Fe3O4@gelatin nanoparticles can be a contrast agent for T2-weighted MRI.

Novel compound heterozygous mutations in ABCA4 in a Chinese pedigree with Stargardt disease.

PURPOSE: Stargardt disease (STGD) is a common macular dystrophy in juveniles that is commonly inherited as an autosomal recessive trait. Mutations in five genes (ABCA4, PROM1, ELOVL4, BEST1, and PRPH2) have been reported to be associated with STGD. In the present study, we aimed to identify the pathogenic mutations in affected members in a Chinese STGD pedigree. METHODS: One patient was selected for whole-exome sequencing. Variants in five candidate genes were identified initially, followed by several filtering steps against public and private variation databases (1000Genomes, ESP6500si, ExAC, and in-house database), as well as bioinformatic analysis of the putative pathogenic roles. Sanger sequencing was used for cosegregation analysis among all members with available DNA. RESULTS: Two mutations in ABCA4 (NM_000350.2; c.5646G>A; p.Met1882Ile and NM_000350.2; c.3523-2A>G) were found using whole-exome sequencing. Cosegregation analysis confirmed all the affected members carried the compound heterozygous mutations while the other healthy members had at most one. The missense mutation was extremely rare in public databases and predicted to be deleterious. The splice-site mutation was absent from all public and private databases and was predicted to alter the splice pattern, resulting in an exon skip and a frameshift. CONCLUSIONS: Using whole-exome sequencing, we found novel compound heterozygous mutations in ABCA4 in a Chinese STGD pedigree. These mutations are reported for the first time, therefore widening the mutation spectrum of Stargardt disease. The present study also illustrates the potential of whole-exome sequencing in determining the genetic cause of STGD.