Influential factors and willingness to advocate for HPV vaccination among male nursing interns in China.

BACKGROUND: Human papillomavirus (HPV) infection significantly contributes to the global cancer burden. Understanding the factors influencing male clinical interns' willingness to promote HPV vaccination is crucial for developing effective public health strategies in China. METHODS: This study employed a stratified random sampling method to select 1,980 male clinical interns from five provinces in China between January and March 2024. Data were collected on participants' demographic characteristics, HPV-related clinical experience, and knowledge. The Theory of Planned Behavior framework, encompassing attitudes, subjective norms, and perceived behavioral control, was used to examine factors influencing the willingness to promote the HPV vaccine. Logistic regression analyses were conducted to identify factors associated with the willingness to promote the HPV vaccine. RESULTS: Among the respondents, 72.29% were willing to encourage others to receive the HPV vaccine. Significant factors influencing this willingness included older age (OR = 3.065, P ≤ 0.001), higher monthly household income (OR = 1.449, P = 0.025), participation in the diagnosis and treatment of HPV-related diseases (OR = 3.458, P ≤ 0.001), positive attitude towards the vaccine (OR = 13.503, P = 0.004), and strong perceived behavioral control (OR = 2.364, P = 0.006). CONCLUSION: This study highlights the critical role of practical experience and targeted education in promoting HPV vaccination among male clinical interns in China. Enhancing the training and education of this group is essential for improving HPV vaccine advocacy and supporting public health efforts to reduce HPV-related diseases.

Does brain-derived neurotrophic factor play a role in the association between maternal prenatal mental health and neurodevelopment in 2-year-old children?

OBJECTIVE: To evaluate the role of brain-derived neurotrophic factor (BDNF)-a crucial modulator of neural development and plasticity-in the association between prenatal maternal anxiety, depression, and perceived stress and child neurodevelopment in a prospective cohort study. METHODS: We included 526 eligible mother-child pairs from the Shanghai Birth Cohort in the study. Maternal mental health was assessed at mid-pregnancy using Zung's Self-Rating Anxiety Scale, Center for Epidemiologic Studies Depression Scale, and Perceived Stress Scale. The concentration of BDNF in cord blood was measured by ELISA. The offspring neurodevelopment at 24 months of age was assessed using the Bayley Scales. Linear and non-linear regression models were used. RESULTS: The average cord blood BDNF levels were higher in female newborns and those born via vaginal delivery, full term, and normal birth weight. Prenatal maternal anxiety (ß = -0.32; 95 % CI: -0.55, -0.09), depression (ß = -0.30; 95 % CI: -0.52, -0.08), and perceived stress (ß = -0.41; 95 % CI: -0.71, -0.12) scores were negatively associated with social-emotional performance at 24 months of age. However, no significant associations were found between prenatal maternal anxiety, depression, or perceived stress at mid-pregnancy and cord blood BDNF levels, as well as between cord blood BDNF levels and child neurodevelopment. LIMITATIONS: Maternal mental health at different timepoints during pregnancy and generalizability of the results warrant further assessment. CONCLUSIONS: Prenatal mental health was not associated with cord blood BDNF level and that BDNF may not be a mediator in the association between prenatal mental health and child neurodevelopment.

Causal associations of birth body size and adult body size with systemic lupus erythematosus: a bidirectional mendelian randomization study.

Objective: Body size is associated with the onset of systemic lupus erythematosus (SLE). However, the evidence for this association is inconclusive. In this study, we aimed to investigate the causal relationship between body size and SLE. Method: We performed a bidirectional Mendelian randomization (MR) analysis that utilized summary statistics sourced from genome-wide association study (GWAS) data obtained from the IEU Open GWAS project website. The inverse variance weighting (IVW) method was used to evaluate the causality, and four additional MR methods were used to supplement the IVW results. Sensitivity analyses were performed using the Cochran's Q test, MR-Egger regression, leave-one-out analysis, and the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test. Results: In the forward direction analysis, the IVW model demonstrated that birth weight (odds ratio (OR), 1.811; 95% confidence interval (CI), 1.174-2.793; p < 0.05) and adult height (OR, 1.225; 95% CI, 1.046-1.434; p < 0.05) were positively associated with SLE. Four additional MR scans were performed parallel to the IVW results. Conversely, SLE was a weak causal factor for increased height (OR, 1.010; 95% CI, 1.002-1.018; p < 0.05) using the IVW method. Heterogeneity, MR-Egger intercept, and leave-one-out analyses indicated that the results were robust. The MR-PRESSO suggested the presence of pleiotropy. Following the exclusion of instrumental variables (IVs) inducing pleiotropy, subsequent MR analysis yielded consistent results, thereby reinforcing the robustness of our findings. Conclusion: Positive causal associations were observed between birth weight, adult height, and SLE incidence. In the reverse analysis, SLE was a weak causal factor for adult height.

Determinants of HPV vaccine uptake intentions in Chinese clinical interns: an extended theory of planned behavior approach.

Background: This study aims to utilize the extended Theory of Planned Behavior (TPB) model to examine the intentions of clinical interns in China towards Human papillomaviruses (HPV) vaccination. It also fills a significant gap in the literature concerning vaccine acceptance in this specific population. Methods: This cross-sectional study was carried out with clinical interns in Shandong Province, China, with a total of 1,619 participants. Data were collected through self-reported questionnaires, including demographic characteristics, TPB variables, and HPV-related health knowledge. Hierarchical regression analysis was employed to identify key factors influencing vaccination intentions, and Structural Equation Modeling (SEM) was used to analyze the interrelationships between these factors. Results: This study initially identified key predictors affecting clinical interns' intentions to receive the HPV vaccine through hierarchical regression analysis. The preliminary model, which accounted for demographic factors, revealed foundational impacts of household income and HPV-related clinical experience on intentions. After integrating TPB variables-attitude, subjective norm, perceived behavioral control, and HPV-related health knowledge-the model's explanatory power was enhanced to 37.30%. SEM analysis focused on the interplay among TPB constructs and extended variables, confirming their significance in forming vaccination intentions, with subjective norm having the most substantial impact (ß = 0.375, p < 0.001). The extended TPB model explained over half of the variance in vaccination intentions, substantiating the hypotheses and revealing the psychological determinants behind clinical interns' decision-making for HPV vaccination. Conclusion: The extended TPB model from this study effectively explains the vaccination intentions among clinical interns for HPV, offering theoretical support for public health strategies and educational interventions targeting this group. These findings are of significant importance for public health practice and future health promotion strategies.

Application of aptamer-conjugated graphene oxide for specific enrichment of microcystin-LR in Achatina fulica prior to matrix-assisted laser desorption ionization mass spectrometry.

Microcystin-LR (MC-LR), as a hepatotoxin, can cause liver swelling, hepatitis, and even liver cancer. In this study, MC-LR aptamer (Apt-3) modified graphene oxide (GO) was designed to enrich MC-LR in white jade snail (Achatina fulica) and pond water, followed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) analysis. Results indicated that the Apt-3/PEG/GO nanocomposites were highly specific to MC-LR, and the detection limit of MALDI-MS was 0.50 ng/mL. Moreover, the MC-LR can be released from nanocomposites at 75°C, thus, the reuse of Apt-3/PEG/GO is realized. Real sample analysis indicated that the Apt-3/PEG/GO nanocomposites coupled with MALDI-MS were efficient in detecting trace amounts of MC-LR in real samples. With the merits of being low cost, reusable, and easy to besynthesized, this Apt-3/PEG/GO MALDI-MS is expected to be comprehensively applied by anchoring suitable aptamers for different targets.

Neuroprotective effect of plasmalogens on AlCl3-induced Alzheimer's disease zebrafish via acting on the regulatory network of ferroptosis, apoptosis and synaptic neurotransmission release with oxidative stress as the center.

Plasmalogens (Pls) are considered to play a potential role in the treatment of neurodegenerative diseases. In the present study, an Alzheimer's disease (AD) model of zebrafish induced by AlCl3 was established to investigate whether the marine-derived Pls could alleviate cognitive impairments of AD zebrafish. Behavioral tests were carried out to assess the athletic ability. The transcriptional profiles of zebrafish in the control, AD model and AD_PLS group were compared and analyzed to determine the potential mechanisms of dietary Pls on AD. The study found that Pls could reverse athletic impairment in the AD zebrafish model, and the expression levels of genes related to ferroptosis, synaptic dysfunction and apoptosis were significantly altered between experimental groups. Further analysis showed that all of these genes were associated with oxidative stress (OS). These data suggest that healthy protective role of marine-derived Pls on AD zebrafish may result from inhibition of ferroptosis and neuronal apoptosis, restoring synaptic neurotransmission release, and reducing neuroinflammation. Among them, Oxidative stress is acted as the center to connect different regulation pathways. This study provides evidence to support the essential roles of OS in pathogenesis of AD, and the application of Pls in relieving AD.

Role of placental barrier on trace element transfer in maternal fetal system and hypertensive disorders complicating pregnancy and gestational diabetes mellitus.

BACKGROUND: Hypertensive disorders complicating pregnancy (HDCP) and gestational diabetes mellitus (GDM) can affect the placental barrier function to varying degrees. However, current studies show that the transfer and distribution characteristics of trace elements in the maternal-fetal system are still unclear. This study investigated the effect of the placental barrier on the transfer of trace elements from mother to fetus and its relationship with HDCP and GDM. METHODS: A case-control method was used in this study. 140 pairs of samples were collected; 60 were from healthy pregnant women, and 80 were from patients with pregnancy complications. The contents of trace elements in paired samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS). SPSS software was used to analyze the differences in trace element levels in matched samples of each group. The correlations were analyzed based on Pearson's correlation factor (r). RESULTS: The distribution characteristics of Fe content in the pathological group (HDCP group and GDM group) were the same as those in the normal group (umbilical cord blood > maternal blood > placenta), but there was no significant difference in the iron content in maternal blood and cord blood of pathological group. The distribution characteristics of Mn content in the pathological group (placenta > umbilical cord blood > maternal blood) were changed compared with those in the normal group (placenta > maternal blood > umbilical cord blood). In addition, the placental Cr content and cord blood Cr and Ni content of the pathological group were higher than those of the normal group. HDCP placental Cr and GDM placental Fe levels were significantly correlated with the Apgar score. CONCLUSIONS: The transfer of Fe and Mn and the placental barrier function of Cr and Ni in the maternal-fetal system of HDCP and GDM are significantly altered, which directly or indirectly increases the maternal and fetal health risk.

Tumor Suppressor Adenomatous Polyposis Coli Sustains Dendritic Cell Tolerance through IL-10 in a ß-Catenin-Dependent Manner.

Dendritic cells (DC) play important roles in balancing immunity and tolerance, in which ß-catenin signaling plays an important role, yet the underlying mechanisms remain elusive. In this study, we investigated the functions of the tumor suppressor adenomatous polyposis coli (APC), also a key component of the ß-catenin upstream destruction complex in DC. APC depletion in DC does not alter DC and T cell homeostasis under resting conditions. However, APC deficiency in DC leads to attenuated antitumor immunity in mice, which exhibit fewer CD8+ T cells and more Foxp3+ regulatory T cells in tumor and draining lymph nodes. Loss of APC in DC does not affect the expression levels of costimulatory molecules. However, APC-deficient DC produce more IL-10 and exhibit a higher ability of inducing regulatory T cells but a lower ability of priming CD8+ T cells, both of which can be reversed by IL-10 inhibition. Lastly, ß-catenin depletion in APC-deficient DC rescues their antitumor immunity and reverses elevated IL-10 production. Taken together, our results identify that APC drives DC tolerance via the ß-catenin/IL-10 axis.

Vps33B controls Treg cell suppressive function through inhibiting lysosomal nutrient sensing complex-mediated mTORC1 activation.

The suppressive function of regulatory T (Treg) cells is tightly controlled by nutrient-fueled mechanistic target of rapamycin complex 1 (mTORC1) activation, yet its dynamics and negative regulation remain unclear. Here we show that Treg-specific depletion of vacuolar protein sorting 33B (Vps33B) in mice results in defective Treg cell suppressive function and acquisition of effector phenotype, which in turn leads to disturbed T cell homeostasis and boosted antitumor immunity. Mechanistically, Vps33B binds with lysosomal nutrient-sensing complex (LYNUS) and promotes late endosome and lysosome fusion and clearance of the LYNUS-containing late endosome/lysosome, and therefore suppresses mTORC1 activation. Vps33B deficiency in Treg cells results in disordered endosome lysosome fusion, which leads to accumulation of LYNUS that causes elevated mTORC1 activation and hyper-glycolytic metabolism. Taken together, our study reveals that Vps33B maintains Treg cell suppressive function through sustaining endolysosomal homeostasis and therefore restricting amino acid-licensed mTORC1 activation and metabolism.

Spatio-Temporal Variation-Induced Group Disparity of Intra-Urban NO2 Exposure.

Previous studies on exposure disparity have focused more on spatial variation but ignored the temporal variation of air pollution; thus, it is necessary to explore group disparity in terms of spatio-temporal variation to assist policy-making regarding public health. This study employed the dynamic land use regression (LUR) model and mobile phone signal data to illustrate the variation features of group disparity in Shanghai. The results showed that NO2 exposure followed a bimodal, diurnal variation pattern and remained at a high level on weekdays but decreased on weekends. The most critical at-risk areas were within the central city in areas with a high population density. Moreover, women and the elderly proved to be more exposed to NO2 pollution in Shanghai. Furthermore, the results of this study showed that it is vital to focus on land-use planning, transportation improvement programs, and population agglomeration to attenuate exposure inequality.

Expanding the mutation and phenotype spectrum of MYH3-associated skeletal disorders.

Pathogenic variants in MYH3 cause distal arthrogryposis type 2A and type 2B3 as well as contractures, pterygia and spondylocarpotarsal fusion syndromes types 1A and 1B. These disorders are ultra-rare and their natural course and phenotypic variability are not well described. In this study, we summarize the clinical features and genetic findings of 17 patients from 10 unrelated families with vertebral malformations caused by dominant or recessive pathogenic variants in MYH3. Twelve novel pathogenic variants in MYH3 (NM_002470.4) were identified: three of them were de novo or inherited in autosomal dominant way and nine were inherited in autosomal recessive way. The patients had vertebral segmentation anomalies accompanied with variable joint contractures, short stature and dysmorphic facial features. There was a significant phenotypic overlap between dominant and recessive MYH3-associated conditions regarding the degree of short stature as well as the number of vertebral fusions. All monoallelic variants caused significantly decreased SMAD3 phosphorylation, which is consistent with the previously proposed pathogenic mechanism of impaired canonical TGF-ß signaling. Most of the biallelic variants were predicted to be protein-truncating, while one missense variant c.4244T>G,p.(Leu1415Arg), which was inherited in an autosomal recessive way, was found to alter the phosphorylation level of p38, suggesting an inhibition of the non-canonical pathway of TGF-ß signaling. In conclusion, the identification of 12 novel pathogenic variants and overlapping phenotypes in 17 affected individuals from 10 unrelated families expands the mutation and phenotype spectrum of MYH3-associated skeletal disorders. We show that disturbances of canonical or non-canonical TGF-ß signaling pathways are involved in pathogenesis of MYH3-associated skeletal fusion (MASF) syndrome.

Heterozygous Recurrent Mutations Inducing Dysfunction of ROR2 Gene in Patients With Short Stature.

PURPOSE: ROR2, a member of the ROR family, is essential for skeletal development as a receptor of Wnt5a. The present study aims to investigate the mutational spectrum of ROR2 in children with short stature and to identify the underlying molecular mechanisms. METHODS: We retrospectively analyzed clinical phenotype and whole-exome sequencing (WES) data of 426 patients with short stature through mutation screening of ROR2. We subsequently examined the changes in protein expression and subcellular location in ROR2 caused by the mutations. The mRNA expression of downstream signaling molecules of the Wnt5a-ROR2 pathway was also examined. RESULTS: We identified 12 mutations in ROR2 in 21 patients, including 10 missense, one nonsense, and one frameshift. Among all missense variants, four recurrent missense variants [c.1675G > A(p.Gly559Ser), c.2212C > T(p.Arg738Cys), c.1930G > A(p.Asp644Asn), c.2117G > A(p.Arg706Gln)] were analyzed by experiments in vitro. The c.1675G > A mutation significantly altered the expression and the cellular localization of the ROR2 protein. The c.1675G > A mutation also caused a significantly decreased expression of c-Jun. In contrast, other missense variants did not confer any disruptive effect on the biological functions of ROR2. CONCLUSION: We expanded the mutational spectrum of ROR2 in patients with short stature. Functional experiments potentially revealed a novel molecular mechanism that the c.1675G > A mutation in ROR2 might affect the expression of downstream Wnt5a-ROR2 pathway gene by disturbing the subcellular localization and expression of the protein.

Fourier Transform Infrared Spectroscopy: An Innovative Method for the Diagnosis of Ovarian Cancer.

Ovarian cancer is the most lethal gynecologic malignancy due to the late diagnoses at advanced stages, drug resistance and the high recurrence rate. Thus, there is an urgent need to develop new techniques to diagnose and monitor ovarian cancer patients. Fourier transform infrared (FTIR) spectroscopy has great potential in the diagnosis of this disease, as well as the real-time monitoring of cancer development and chemoresistance. As a noninvasive, simple and convenient technique, it can not only distinguish the molecular differences between normal and malignant tissues, but also be used to identify the characteristics of different types of ovarian cancer. FTIR spectroscopy is also widely used in monitoring cancer cells in response to antitumor drugs, distinguishing cells in different growth states, and identifying new synthetic drugs. In this paper, the applications of FTIR spectroscopy for ovarian cancer diagnosis and other works carried out so far are described in detail.

miR­199a­3p suppresses cervical epithelial cell inflammation by inhibiting the HMGB1/TLR4/NF­κB pathway in preterm birth.

Preterm birth (PTB) is the primary cause of neonatal mortality worldwide. Infection and inflammation are considered to be the primary causes of PTB. Cervical remodeling is an important step in the process of preterm delivery, and the destruction of the cervical epithelial barrier and inflammation are important triggers of cervical remodeling. The aim of the present study was to determine the effect and underlying mechanism of microRNA (miR)­199a­3p/high­mobility group box 1 protein (HMGB1) signaling in cervical epithelial inflammation in PTB. The results of this study revealed that miR­199a­3p was significantly decreased in cervical epithelial tissue samples from patients in both the preterm labor and preterm premature rupture of membrane groups. This decrease was also observed in tissue samples from a lipopolysaccharide (LPS)­induced PTB mouse model and in LPS­induced ectocervical and endocervical cells. Whereas, the expression of HMGB1 and toll­like receptor 4 (TLR4) was significantly increased, which was associated with the upregulation of interleukin (IL)­1ß and tumor necrosis factor (TNF)­α expression. Furthermore, overexpression of miR­199a­3p significantly suppressed the expression and activation of HMGB1 and TLR4/NF­κB signaling, and decreased the levels of IL­1ß and TNF­α in vitro and in vivo. Additionally, overexpression of HMGB1 and/or TLR4 reversed the anti­inflammatory effects of miR­199a­3p mimics in vitro and in vivo. These results indicate that miR­199a­3p acts as a negative inflammatory regulator in PTB by targeting HMGB1 to regulate the TLR4/NF­κB pathway.

The mutational burden and oligogenic inheritance in Klippel-Feil syndrome.

BACKGROUND: Klippel-Feil syndrome (KFS) represents a rare anomaly characterized by congenital fusion of the cervical vertebrae. The underlying molecular etiology remains largely unknown because of the genetic and phenotypic heterogeneity. METHODS: We consecutively recruited a Chinese cohort of 37 patients with KFS. The clinical manifestations and radiological assessments were analyzed and whole-exome sequencing (WES) was performed. Additionally, rare variants in KFS cases and controls were compared using genetic burden analysis. RESULTS: We primarily examined rare variants in five reported genes (GDF6, MEOX1, GDF3, MYO18B and RIPPLY2) associated with KFS and detected three variants of uncertain significance in MYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D. In addition, seven patients were proposed to show potential oligogenic inheritance involving more than one variants in candidate genes, the frequency of which was significantly higher than that in the in-house controls. CONCLUSIONS: Our study presents an exome-sequenced cohort and identifies five novel genes potentially associated with KFS, extending the spectrum of known mutations contributing to this syndrome. Furthermore, the genetic burden analysis provides further evidence for potential oligogenic inheritance of KFS.

Mutational landscape and genetic signatures of cell-free DNA in tumour-induced osteomalacia.

Tumour-induced osteomalacia (TIO) is a very rare paraneoplastic syndrome with bone pain, fractures and muscle weakness, which is mostly caused by phosphaturic mesenchymal tumours (PMTs). Cell-free DNA (cfDNA) has been regarded as a non-invasive liquid biopsy for many malignant tumours. However, it has not been studied in benign tumours, which prompted us to adopt the targeted next-generation sequencing approach to compare cfDNAs of 4 TIO patients, four patients with bone metastasis (BM) and 10 healthy controls. The mutational landscapes of cfDNA in TIO and BM groups were similar in the spectrum of allele frequencies and mutation types. Markedly, deleterious missense mutations in FGFR1 and loss-of-function mutations in MED12 were found in 3/4 TIO patients but none of BM patients. The gene ontology analysis strongly supported that these mutated genes found in TIOs would play a potential role in PMTs' process. The genetic signatures and corresponding change in expression of FGFR1 and FGF23 were further validated in PMT tissues from a test cohort of another three TIO patients. In summary, we reported the first study of the mutational landscape and genetic signatures of cfDNA in TIO/PMTs.

Fourier Transform Infrared Spectroscopy Monitoring of Dihydroartemisinin-Induced Growth Inhibition in Ovarian Cancer Cells and Normal Ovarian Surface Epithelial Cells.

PURPOSE: Ovarian cancer is the most lethal of gynecological malignancies. Dihydroartemisinin (DHA), a derivative of artemisinin (ARS), has profound effects against human tumors. The aim of this study was to provide a convenient, cost-efficient technique, Fourier transform infrared (FTIR) spectroscopy, to monitor and evaluate responses to DHA-induced growth inhibition of ovarian cancer cells. METHODS: Cell growth and viability and the 50% inhibitory concentration (IC50) of DHA were assessed by the MTT assay. FTIR spectroscopy was used to monitor cells following DHA treatment, and data were analyzed by OMNIC 8.0 software. RESULTS: DHA can decrease the viability of ovarian cancer cells and normal cells, but cancer cells were more sensitive to this drug than normal cells. Spectral differences were observed between cells with or without DHA treatment. In particular, an increase in the amount of lipids and nucleic acids was observed. The band intensity ratio of 1454/1400, and the intensity of the band 1741 cm-1 increased, indicating stronger absorption after DHA treatment. Moreover, the differences were larger for the cell lines that were more sensitive to DHA. CONCLUSION: The spectral features provided information about important molecular characteristics of the cells in response to chemicals. These findings demonstrated the possible use of FTIR spectroscopy to evaluate DHA-induced growth inhibition effects in ovarian cancer cells and provided a promising new tool for monitoring cell growth and the effects of antitumor drugs in the clinic in the future.

Exome sequencing reveals a novel variant in NFX1 causing intracranial aneurysm in a Chinese family.

BACKGROUND: Genetic risk factors play an important role in the pathogenesis of familial intracranial aneurysms (FIAs); however, the molecular mechanisms remain largely unknown. OBJECTIVE: To investigate potential FIA-causing genetic variants by rare variant interrogation and a family-based genomics approach in a large family with an extensive multigenerational pedigree with FIAs. METHOD: Exome sequencing (ES) was performed in a dominant likely family with intracranial aneurysms (IAs). Variants were analyzed by an in-house developed pipeline and prioritized using various filtering strategies, including population frequency, variant type, and predicted variant pathogenicity. Sanger sequencing was also performed to evaluate the segregation of the variants with the phenotype. RESULTS: Based on the ES data obtained from five individuals from a family with 7/21 living members affected with IAs, a total of 14 variants were prioritized as candidate variants. Familial segregation analysis revealed that NFX1 c.2519T>C (p.Leu840Pro) segregated in accordance with Mendelian expectations with the phenotype within the family-that is, present in all IA-affected cases and absent from all unaffected members of the second generation. This missense variant is absent from public databases (1000genome, ExAC, gnomAD, ESP5400), and has damaging predictions by bioinformatics tools (Gerp ++ score = 5.88, CADD score = 16.43, MutationTaster score = 1, LRT score = 0). In addition, 840Leu in NFX1 is robustly conserved in mammals and maps in a region before the RING-type zinc finger domain. CONCLUSION: NFX1 c.2519T>C (p.Leu840Pro) may contribute to the pathogenetics of a subset of FIAs.