Contribution of the transcription factor SfGATAe to Bt Cry toxin resistance in Spodoptera frugiperda through reduction of ABCC2 expression.

Insect resistance evolution poses a significant threat to the advantages of biopesticides and transgenic crops utilizing insecticidal Cry-toxins from Bacillus thuringiensis (Bt). However, there is limited research on the relationship between transcriptional regulation of specific toxin receptors in lepidopteran insects and their resistance to Bt toxins. Here, we report the positive regulatory role of the SfGATAe transcription factor on the expression of the ABCC2 gene in Spodoptera frugiperda. DNA regions in the SfABCC2 promoter that are vital for regulation by SfGATAe, utilizing DAP-seq technology and promoter deletion mapping. Through yeast one-hybrid assays, DNA pull-down experiments, and site-directed mutagenesis, we confirmed that the transcription factor SfGATAe regulates the core control site PBS2 in the ABCC2 target gene. Tissue-specific expression analysis has revealed that SfGATAe is involved in the regulation and expression of midgut cells in the fall armyworm. Silencing SfGATAe in fall armyworm larvae resulted in reduced expression of SfABCC2 and decreased sensitivity to Cry1Ac toxin. Overall, this study elucidated the regulatory mechanism of the transcription factor SfGATAe on the expression of the toxin receptor gene SfABCC2 and this transcriptional control mechanism impacts the resistance of the fall armyworm to Bt toxins.

A Thiol Branched 3D Network Quasi Solid-State Polymer Electrolyte Reinforced by Covalent Organic Frameworks for Lithium Metal Batteries.

Quasi solid-state polymer electrolytes (QSPEs) are particularly attractive due to their high ionic conductivity and excellent safety for lithium metal batteries (LMBs). However, it is still a great challenge for QSPEs to achieve strong mechanical strength and high electrochemical performance simultaneously. Herein, a QSPE (SCOF-PEP-PEA) using a covalent organic framework (COF) containing abundant allyl groups (SCOF) as a rigid porous filler as well as a cross-linker to reinforce the polymer network is reported. Benefitting from the unique 3D nanonetwork structure and abundant lithiophilic functional groups, SCOF-PEP-PEA QSPE exhibits high ionic conductivity (4.0 × 10-4 S cm-1) and high lithium-ion transference number (0.82) at room temperature. Moreover, SCOF-PEP-PEA QSPE displays much improved mechanical strength compared to PEP-PEA QSPE (AFM Young's modulus: 453 vs 36 MPa). As a result, the Li/LFP full cell with SCOF-PEP-PEA QSPE shows great rate performance of 141 mAh g-1 at 1C and delivers a high specific capacity retention of 92% after 220 cycles at 0.5 C (60 °C). This work provides a new strategy to design and prepare high-performance QSPEs with COFs as porous organic filler, and further expand the application of COFs for energy storage applications.

Overexpression of LINC00853 enhances tumorigenesis and metastasis of gastric cancer.

Gastric cancer (GC) is a rising global health issue, with increasing incidence and mortality rates. The pathogenesis of GC is highly complex and involves a combination of genetic and environmental factors. Therefore, identifying new genes and pathways that contribute to the development and progression of GC is essential for improving diagnosis and treatment outcomes. Long noncoding RNAs (lncRNAs) have recently emerged as a promising area of research in understanding the molecular mechanisms underlying various cancers, including GC. These RNA molecules are longer than 200 nucleotides and do not code proteins. Although initially considered "junk DNA", lncRNAs have been demonstrated to play significant roles in various biological processes, including cell proliferation, differentiation, and apoptosis, as well as in the pathogenesis of various cancers. In this study, we screened clinical specimens for a novel lncRNA, LINC00853, which showed high expression in GC tissues and promoted the proliferation, migration, and invasion of GC cells. Furthermore, in vivo experiments confirmed its ability to facilitate the growth and metastasis of GC. These results suggest that LINC00853 plays a crucial role in the development and progression of GC.

LINC01852 inhibits the tumorigenesis and chemoresistance in colorectal cancer by suppressing SRSF5-mediated alternative splicing of PKM.

BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, and chemoresistance is a major obstacle in its treatment. Despite advances in therapy, the molecular mechanism underlying chemoresistance in CRC is not fully understood. Recent studies have implicated the key roles of long noncoding RNAs (lncRNAs) in the regulation of CRC chemoresistance. METHODS: In this study, we investigated the role of the lncRNA LINC01852 in CRC chemoresistance. LINC01852 expression was evaluated in multiple CRC cohorts using quantitative reverse transcription PCR. We conducted in vitro and in vivo functional experiments using cell culture and mouse models. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of LINC01852 in CRC. RESULTS: Our findings revealed that a lncRNA with tumor-inhibiting properties, LINC01852, was downregulated in CRC and inhibited cell proliferation and chemoresistance both in vitro and in vivo. Further mechanistic investigations revealed that LINC01852 increases TRIM72-mediated ubiquitination and degradation of SRSF5, inhibiting SRSF5-mediated alternative splicing of PKM and thereby decreasing the production of PKM2. Overexpression of LINC01852 induces a metabolic switch from aerobic glycolysis to oxidative phosphorylation, which attenuates the chemoresistance of CRC cells by inhibiting PKM2-mediated glycolysis. CONCLUSIONS: Our results demonstrate that LINC01852 plays an important role in repressing CRC malignancy and chemoresistance by regulating SRSF5-mediated alternative splicing of PKM, and that targeting the LINC01852/TRIM72/SRSF5/PKM2 signaling axis may represent a potential therapeutic strategy for CRC.

Association of baseline and dynamic arterial stiffness status with dyslipidemia: a cohort study.

Background and aims: Dyslipidemia is known to contribute to arterial stiffness, while the inverse association remains unknown. This study aimed to explore the association of baseline arterial stiffness and its changes, as determined by brachial-ankle pulse wave velocity (baPWV), with dyslipidemia onset in the general population. Methods: This study enrolled participants from Beijing Health Management Cohort using measurements of the first visit from 2012 to 2013 as baseline, and followed until the dyslipidemia onset or the end of 2019. Unadjusted and adjusted Cox proportional regression models were used to evaluate the associations of baseline baPWV and baPWV transition (persistent low, onset, remitted and persistent high) with incident dyslipidemia. Results: Of 4362 individuals (mean age: 55.5 years), 1490 (34.2%) developed dyslipidemia during a median follow-up of 5.9 years. After adjusting for potential confounders, participants with elevated arterial stiffness at baseline had an increased risk of dyslipidemia (HR, 1.194; 95% CI, 1.050-1.358). Compared with persistent low baPWV, new-onset and persistent high baPWV were associated with a 51.2% and 37.1% excess risk of dyslipidemia. Conclusion: The findings indicated that arterial stiffness is an early risk factor of dyslipidemia, suggesting a bidirectional association between arterial stiffness and lipid metabolism.

OGM and WES identifies translocation breakpoints in PKD1 gene in an polycystic kidney patient and healthy baby delivered using PGT.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common autosomal dominant genetic diseases. Whole exome sequencing (WES) is a routine tool for diagnostic confirmation of genetic diseases, and it is usually performed to confirm the clinical diagnosis in ADPKD. Reciprocal translocation is the most common chromosomal structural abnormalities and most of its carriers have normal phenotypes until they are encountered infertility problems in adulthood. However, for the polycystic kidney disease caused by abnormal chromosome structure, WES is difficult to achieve the purpose of gene diagnosis. METHODS: ADPKD-related genes were detected by WES; Chromosomal karyotyping and Optical Genome Mapping (OGM) were used to detect structural variant; The genomic break-point locations and the abnormal splicing were detected by reverse transcription-PCR and Sanger sequencing; The karyomapping gene chip and Next-Generation Sequencing (NGS) were performed to screen aneuploidy and to distinguish the non-carrier embryos from the carrier embryos. RESULTS: No pathogenic variant was found after the first round of WES analysis. Karyotyping data showed 46, XX, t (16; 17) (p13.3; q21.3). With the help of OGM, the translocation breakpoint on chromosome 16 was located within the PKD1 gene. With re-analysis of WES raw data, the breakpoint of translocation was verified to be located at the c.10618 + 3 of PKD1 gene. Based on this molecular diagnosis, a non-carrier embryo was selected out from three blastocysts. With preimplantation genetic testing (PGT) after in vitro fertilization (IVF), it was then transferred into uterus. With confirmation by prenatal and postnatal testing, the pedigree delivered a healthy baby. CONCLUSION: We identified a case of ADPKD caused by balanced translocation and assisted the patient to have a healthy child. When the phenotype was closely related with a monogenic disease and the WES analysis was negative, chromosomal structural analysis would be recommended for further genetic diagnosis. Based on the precision diagnosis, preventing the recurrence of hereditary diseases in offspring would be reachable.

Up-regulation of STRA6 predicts poor prognosis and contributes to oxaliplatin resistance in colorectal cancer.

Signaling receptor and transporter of retinol STRA6 (STRA6) plays a primary role in transporting retinol. Several studies have reported that STRA6 is involved in several pathways related to tumorigenesis and progression. However, the exact functions and mechanisms of STRA6 in colorectal cancer (CRC) remain unclear. In our work, STRA6 was highly up-regulated in CRC and promoted the proliferation of CRC cells. Additionally, we discovered that STRA6 suppresses apoptosis partly by controlling BCL2 expression, which in turn causes CRC to become resistant to LOHP treatment. Our study demonstrates that STRA6 is a potential prognostic factor and oncogene in CRC by promoting CRC growth and chemoresistance.

Variations in mitochondrial DNA coding and D-loop region are associated with early embryonic development defects in infertile women.

Mitochondrial DNA (mtDNA) plays a critical role in oocyte maturation, fertilization, and early embryonic development. Defects in mtDNA may determine the alteration of the mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply, leading to impaired oocyte maturation, abnormal fertilization, and low embryonic developmental potential, ultimately leading to female infertility. This case-control study was established to investigate the correlation between mtDNA variations and early embryonic development defects. Peripheral blood was collected for next-generation sequencing from women who suffered the repeated failures of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) cycles due to early embryonic development defects as well as in-house healthy controls, and the sequencing results were statistically analyzed for all subjects. This study found that infertile women with early embryonic development defects carried more mtDNA variants, especially in the D-loop region, ATP6 gene, and CYTB gene. By univariate logistic regression analysis, 16 mtDNA variants were associated with an increased risk of early embryonic development defects (OR > 1, p < 0.05). Furthermore, we identified 16 potentially pathogenic mtDNA variants only in infertile cases. The data proved that mtDNA variations were associated with early embryonic development defects in infertile Chinese women.

MicroRNA-204-5p: A pivotal tumor suppressor.

MicroRNAs (miRNAs) are a class of non-coding single-stranded RNA molecules with a length of approximately 18-25 nt nucleotides that regulate gene expression post-transcriptionally. MiR-204-5p originates from the sixth intron of the transient receptor potential cation channel subfamily M member 3 (TRPM3) gene. MiR-204-5p is frequently downregulated in various cancer types and is related to the clinicopathological characteristics and prognosis of cancer patients. So far, many studies have determined that miR-204-5p functions as a tumor suppressor for its extensive and powerful capacity to inhibit tumor proliferation, metastasis, autophagy, and chemoresistance in multiple cancer types. MiR-204-5p appears to be a promising prognostic biomarker and a therapeutic target for human cancers. This review summarized the latest advances on the role of miR-204-5p in human cancers.

Low-dose radiotherapy promotes the formation of tertiary lymphoid structures in lung adenocarcinoma.

Purpose: A tertiary lymphoid structure (TLS) refers to an organized infiltration of immune cells that is linked to a positive prognosis and improved response to immunotherapy. However, methods that promote TLS formation are limited and challenging to implement in clinical settings. In this study, we aimed to promote the formation and maturation of TLSs in lung adenocarcinoma (LUAD) by combining low-dose radiotherapy (LDRT) with immunotherapy. Methods: Tissue sections from 198 patients who had undergone surgery were examined. Risk factors for patient survival were assessed, and the relationship between TLSs and five-year survival was analyzed. The Kras-LSL-G12D spontaneous lung cancer mouse model was used to screen the optimal irradiation dose (0/1/2 Gy whole lung irradiation) for promoting TLS formation. LDRT combined with anti-PD-1 was used to promote the formation and maturation of TLSs. Results: TLS+, TLSHigh, TLS+GC+ and CD8High within TLS+ were associated with a favorable prognosis. LDRT increased the formation of early TLSs in the Kras-LSL-G12D lung cancer mouse model. In addition, LDRT combined with anti-PD-1 treatment can significantly improve the maturity of TLSs in mouse LUAD, resulting in greater antitumor effects. This antitumor effect was strongly associated with the number of CD8+ T cells within the TLSs. Conclusion: We successfully applied LDRT combined with PD-1 inhibitor therapy for the first time, which increased both the quantity and maturity of TLSs in lung cancer. This approach achieved a promising antitumor effect.

Analysis of rhizosphere bacterial communities of tobacco resistant and non-resistant to bacterial wilt in different regions.

Tobacco bacterial wilt has seriously affected tobacco production. Ethyl methanesulfonate (EMS) induced tobacco bacterial wilt resistant mutants are important for the control of tobacco bacterial wilt. High-throughput sequencing technology was used to study the rhizosphere bacterial community assemblages of bacterial wilt resistant mutant tobacco rhizosphere soil (namely KS), bacterial wilt susceptible tobacco rhizosphere soil (namely GS) and bulk soil (namely BS) in Xuancheng, Huanxi, Yibin and Luzhou. Alpha analysis showed that the bacterial community diversity and richness of KS and GS in the four regions were not significantly different. However, analysis of intergroup variation in the top 15 bacterial communities in terms of abundance showed that the bacterial communities of KS and GS were significantly different from BS, respectively. In addition, pH, alkali-hydrolysable nitrogen (AN) and soil organic carbon (SOC) were positively correlated with the bacterial community of KS and negatively correlated with GS in the other three regions except Huanxi. Network analysis showed that the three soils in the four regions did not show a consistent pattern of network complexity. PICRUSt functional prediction analysis showed that the COG functions were similar in all samples. All colonies were involved in RNA processing and modification, chromatin structure and dynamics, etc. In conclusion, our experiments showed that rhizosphere bacterial communities of tobacco in different regions have different compositional patterns, which are strongly related to soil factors.

[Analysis of novel compound heterozygous variants of the GJA8 gene in a child with congenital cataract].

OBJECTIVE: To explore the genetic basis for child with congenital cataract. METHODS: The child was subjected to next-generation sequencing. Candidate variant was verified by Sanger sequencing of his family members. RESULTS: The proband was found to harbor novel heterozygous variants of c.855del and c.872dup of the GJA8 gene, which were inherited from his father and mother, respectively. Neither of these two variants has been reported. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.855del and c.872dup variants were classified as likely pathogenic (PVS1_S+PM2+PP4) and pathogenic (PVS1_S+PM2+PM3+PP4), respectively. CONCLUSION: The c.855del and c.872dup variants of the GJA8 gene probably underlay the congenital cataract in this patient.

Metabolomic and transcriptomic analysis of roots of tobacco varieties resistant and susceptible to bacterial wilt.

Ralstonia solanacearum severely damages the growth of tobacco (Nicotiana tabacum L.) and causes great economic losses in tobacco production. To investigate the root metabolism and transcriptional characteristics of tobacco bacterial wilt susceptible variety Cuibi-1 (CB-1) and resistant new line KCB-1 (derived from an ethyl methanesulfonate (EMS) mutant of CB-1) after infestation with R. solanacearum, root metabolism and transcriptional characteristics were investigated using RNA-Seq and liquid chromatography-mass spectrometry (LC-MS). Differences in resistance between KCB-1 and CB-1 were observed in several aspects: (1) The phenylpropanoid pathway was the main pathway of resistance to bacterial wilt in KCB-1 compared with CB-1. (2) KCB-1 had more differential metabolic markers of disease resistance than CB-1 after infection with R. solanacearum. Among them, the differential coumarin-like metabolites that affect quorum sensing (QS) and biofilm formation of R. solanacearum differ in KCB-1 and CB-1. (3) KCB-1 inhibited production of the R. solanacearum metabolite putrescine, and the level of putrescine in tobacco was positively correlated with susceptibility. (4) Compared with CB-1, the metabolites of KCB-1 had less differential nitrogen sources during the infestation of R. solanacearum, which was detrimental to the growth and reproduction of R. solanacearum. (5) Both indole-3-acetic acid (IAA) and abscisic acid (ABA) in CB-1 and KCB-1 were involved in the response to R. solanacearum infestation, but the levels of IAA and ABA in KCB-1 were greater than in CB-1 at 24 h post inoculation (hpi). In conclusion, R. solanacearum caused reprogramming of both root metabolism and transcription in KCB-1 and CB-1, and the transcriptional and metabolic characteristics of resistant tobacco were more unfavorable to R. solanacearum.

[Advances in receptor-mediated resistance mechanisms of Lepidopteran insects to Bacillus thuringiensis toxin].

Bacillus thuringiensis is widely used as an insecticide which is safe and environmentally friendly to humans and animals. One of the important insecticidal mechanisms is the binding of Bt toxins to specific toxin receptors in insect midgut and forming a toxin perforation which eventually leads to insect death. The resistance of target pests to Bt toxins is an important factor hampering the long-term effective cultivation of Bt crops and the continuous use of Bt toxins. This review summarizes the mechanism of insect resistance to Bt toxins from the perspective of important Bt toxin receptors in midgut cells of Lepidopteran insects, which may facilitate the in-depth study of Bt resistance mechanism and pest control.

Emerging porous organic polymers for biomedical applications.

Porous organic polymers (POPs) have emerged as a new class of multifunctional porous materials and received tremendous research attention from both academia and industry. Most POPs are constructed from versatile organic small molecules with diverse linkages through strong covalent bonds. Owing to their high surface area and porosity, low density, high stability, tunable pores and skeletons, and ease of functionalization, POPs have been extensively studied for gas storage and separation, heterogeneous catalysis, biomedicine, sensing, optoelectronics, energy storage and conversion, etc. Particularly, POPs are excellent platforms with exciting opportunities for biomedical applications. Consequently, considerable efforts have been devoted to preparing POPs with an emphasis on their biomedical applications. In this review, first, we briefly describe the different subclasses of POPs and their synthetic strategies and functionalization approaches. Then, we highlight the state-of-the-art progress in POPs for a variety of biomedical applications such as drug delivery, biomacromolecule immobilization, photodynamic and photothermal therapy, biosensing, bioimaging, antibacterial, bioseparation, etc. Finally, we provide our thoughts on the fundamental challenges and future directions of this emerging field.

[Identification of a novel variant of NHS gene underlying Nance-Horan syndrome].

OBJECTIVE: To explore the genetic basis for a pedigree affected with Nance-Horan syndrome. METHODS: Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity. RESULTS: A small insertional variant c.766dupC (p.Leu256Profs*21) of the NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+PM2+PM6+PP4). CONCLUSION: The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.

High-Performance NixCo3-xO4/Ti3C2Tx-HT Interfacial Nanohybrid for Electrochemical Overall Water Splitting.

This study highlights the facet structure control of regular NixCo3-xO4 nanoplates and interfacial modulation through elemental doping and morphologically fitted assembly of Ti3C2Tx nanosheets for high performances in OER/HER and overall water splitting. Over the resulting Ni0.09Co2.91O4/Ti3C2Tx-HT in a solution of 1 M KOH, the OER and HER overpotentials of 262 and 210 mV, respectively, are achievable at a current density of 10 mA cm-2. In the case of the overall water splitting by using Ni0.09Co2.91O4/Ti3C2Tx-HT as anode and cathode catalysts, only a potential of 1.66 V is needed to obtain a current density of 10 mA cm-2, and the catalysts can stand for a period of 70 h, remarkably outperforming the RuO2-Pt/C-based catalyst and benefiting from the intensive association and interfacial function between the Ti3C2Tx and NixCo3-xO4 nanosheets. Interestingly, a surface reconstruction from the (112) to (111) facet structure occurred upon the fine-tuned Ni doping of regular NixCo3-xO4 hexagonal nanoplates and led to a highly active catalyst surface. At x = 0.09, the amount of Ni3+ becomes the highest, which is favorable for the generation of the critical OH intermediates on NixCo3-xO4/Ti3C2Tx-HT. The current study documented the significance of the well-controlled interfacial assembly of transition-metal oxide/MXenes as an effective electrocatalyst in the OER/HER and overall water splitting processes and provided the insights into the structure-performance correlation over such kinds of precious metal-free catalysts.

[A case of tuberous sclerosis complex due to a novel splicing variant of TSC2 gene].

OBJECTIVE: To explore the genetic basis for a patient with tuberous sclerosis complex. METHODS: Genomic DNA was extracted from peripheral blood samples from members of his family and 100 unrelated healthy controls. The proband was subjected to next-generation sequencing, and candidate variant was confirmed by multiple ligation-dependent probe amplification (MLPA) and Sanger sequencing. Reverse transcription-PCR (RT-PCR) was carried out to determine the relative mRNA expression in the proband. RESULTS: The patient was found to harbor a c.2355+1G>C splicing variant of the TSC2 gene. Sequencing of cDNA confirmed that 62 bases have been inserted into the 3' end of exon 21, which has caused a frameshift producing a truncated protein. CONCLUSION: The novel splicing variant c.2355+1G>C of the TSC2 gene probably underlay the TSC in the proband. Above finding has expanded the variant spectrum of TSC2 and provided a basis for preimplantation genetic testing and/or prenatal diagnosis.

Polyvinyl chloride gels microlens array with a well-controlled curvature obtained by solvent evaporation under DC electric fields.

In this paper, polyvinyl chloride (PVC) gels microlens arrays (MLAs) with controllable curvatures were prepared by evaporation of the solvent under DC electric fields. In order to obtain these arrays, the PVC gel solution was first injected into the cofferdam of a ring array patterned electrode substrate. Upon polarization under DC electric field, the electric charge injected from the cathode was carried by the plasticizers towards the anode to accumulate on its surface. After complete evaporation of the solvent, the PVC gels formed stable MLAs. The focal length of the formed MLAs obtained after evaporation of the 100 µL PVC gel solvent under 30 V DC field was 8.68 mm. The focal length of the as-obtained PVC gel-based MLAs can be well-controlled by merely tuning the strength of the electric field or by changing the volume of the PVC gel solution. Thus, it can be concluded that the proposed methodology looks very promising for future fabrication of MLAs with uniform size in larger areas.

A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report.

BACKGROUND: Marfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1-0.2‰. The causative variant of FNB1 gene accounts for approximately 70-80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene. This finding extended the variant spectrum of the FBN1 gene and will provide a solution for patients to bear healthy offspring by preimplantation genetic testing or prenatal diagnosis. CASE PRESENTATION: The patient was treated due to tachycardia during excitement in a hospital. Echocardiography showed dilatation of the ascending aorta and main pulmonary artery, mitral regurgitation (mild), tricuspid regurgitation (mild), and abnormal left ventricular filling. Electrocardiograph showed sinus rhythm. In addition, flutters of shadows in front of his eyes and vitreous opacity were present in the patient. Genomic DNA was extracted from peripheral blood samples from members of the family and 100 unrelated controls. Potential variants were screened out by next-generation sequencing and confirmed by MLPA & Sanger sequencing. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the relative mRNA quantitation in the patient. A heterozygous nonsense variant c.3217G > T of the FBN1 gene, which resulted in p. Glu1073Term, was identified in both patients. Only wild type bases were found in the cDNA sequence of the patient. Real-time fluorogenic quantitative PCR results showed that the relative expression level of FBN1 cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of the FBN1 gene introduces a Stop codon in the cb-EGF12 domain. We speculated that a premature translational-termination codon (PTC) was located in the mRNA and the target mRNA was disintegrated through a process known as nonsense-mediated mRNA decay (NMD), which led to a significant decrease of the fibrillin-1 protein, eventually causing clinical symptoms in the patient. CONCLUSIONS: In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene, which eventually led to Marfan syndrome in a Chinese family.