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PURPOSE: Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders, resulting in blindness in children. This study aimed to describe the clinical and genetic characteristics of a cohort of patients with LCA and to investigate the retinal vascular characteristics in LCA patients. METHODS: Fifty-two children with LCA were included in the study. All patients underwent detailed ocular examinations. Electroretinography (ERG) was used to evaluate the retinal function. Optical coherence tomography (OCT) was used to assess the structure change of the retina for those patients who were able to cooperate very well. Panel-based next-generation sequencing was performed to identify pathogenic variants in genes associated with LCA. Diameters of the retinal vessels were measured using the EVision AI screening system with an artificial intelligence (AI) technique. An ultrasound Doppler was used to evaluate hemodynamic parameters, including peak systolic velocity (PSV), resistive index (RI), and pulsatility index (PI), in the ophthalmic, central retinal, posterior ciliary, carotid, and internal carotid as well as external carotid arteries in 12 patients aged from 3 to 14 years. RESULTS: We detected 75 pathogenic variants from ten genes of RPGRIP1, CEP290, GUCY2D, LCA5, AIPL1, CRB1, RPE65, CRX, RDH12, and TULP1, including 29 novel and 36 previously reported variants in 52 affected children with LCA, with the highest detective rate in RPGRIP1 (26.9%). Fundus appearance is diverse in patients with LCA, ranging from normal to severe peripheral or central retinopathy. Retinal vasculature was evaluated in 12 patients with different gene variants, showing narrowed arteries with an average diameter of 43.6 ± 3.8 µm compared to that of 51.7 ± 2.6 µm in the normal controls (P < 0.001, n = 12). Meanwhile, their hemodynamic parameters were changed as well in the ophthalmic artery (OA), with a decreased PSV (P = 0.0132, n = 12) and slightly increased PI (P = 0.0488, n = 12) compared to the normal controls. However, the hemodynamic parameters did not change significantly in the other vessels. CONCLUSIONS: Blood supply to the eyeball is predicted to be reduced in patients with LCA, presumably due to photoreceptor cell degeneration. The novel identified variants will expand the spectrum of variants in LCA-related genes and be useful for studying the molecular mechanisms of LCA.
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OBJECTIVE: To investigate the characteristics of eye movement in children with anisometropic amblyopia, and to compare those characteristics with eye movement in a control group. METHODS: 31 children in the anisometropic amblyopia group (31 amblyopic eyes in group A, 31 contralateral eyes in group B) and 24 children in the control group (48 eyes in group C). Group A was subdivided into groups Aa (severe amblyopia) and Ab (mild-moderate amblyopia). The overall age range was 6-12 years (mean, 7.83 ± 1.79 years). All children underwent ophthalmic examinations; eye movement parameters including saccade latency and amplitude were evaluated using an Eyelink1000 eye tracker. Data Viewer and MATLAB software were used for data analysis. RESULTS: Mean and maximum saccade latencies, as well as mean and maximum saccade amplitudes, were significantly greater in group A than in groups B and C before and after treatment (P < 0.05). Mean and maximum saccade latencies were significantly different among groups Aa, Ab, and C (P < 0.05). Pupil trajectories in two detection modes suggested that binocular fixation was better than monocular fixation. CONCLUSIONS: Eye movement parameters significantly differed between contralateral normal eyes and control eyes. Clinical evaluation of children with anisometropic amblyopia should not focus only on static visual acuity, but also on the assessment of eye movement.
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Ambliopia , Visão Binocular , Acuidade Visual , Humanos , Ambliopia/fisiopatologia , Criança , Masculino , Feminino , Acuidade Visual/fisiologia , Visão Binocular/fisiologia , Movimentos Sacádicos/fisiologia , Movimentos Oculares/fisiologia , Anisometropia/fisiopatologia , Anisometropia/complicações , Fixação Ocular/fisiologiaRESUMO
BACKGROUND: Congenital stationary night blindness (CSNB) is an inherited retinal disorder. Most of patients have myopia. This study aims to describe the clinical and genetic characteristics of fifty-nine patients with CSNB and investigate myopic progression under genetic cause. RESULTS: Sixty-five variants were detected in the 59 CSNB patients, including 32 novel and 33 reported variants. The most frequently involved genes were NYX, CACNA1F, and TRPM1. Myopia (96.61%, 57/59) was the most common clinical finding, followed by nystagmus (62.71%, 37/59), strabismus (52.54%, 31/59), and nyctalopia (49.15%, 29/59). An average SE of -7.73 ± 3.37 D progressed to -9.14 ± 2.09 D in NYX patients with myopia, from - 2.24 ± 1.53 D to -4.42 ± 1.43 D in those with CACNA1F, and from - 5.21 ± 2.89 D to -9.24 ± 3.16 D in those with TRPM1 during the 3-year follow-up; the TRPM1 group showed the most rapid progression. CONCLUSIONS: High myopia and strabismus are distinct clinical features of CSNB that are helpful for diagnosis. The novel variants identified in this study will further expand the knowledge of variants in CSNB and help explore the molecular mechanisms of CSNB.
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Oftalmopatias Hereditárias , Doenças Genéticas Ligadas ao Cromossomo X , Miopia , Cegueira Noturna , Estrabismo , Canais de Cátion TRPM , Humanos , Cegueira Noturna/genética , Miopia/genética , Retina , Canais de Cátion TRPM/genéticaRESUMO
OBJECTIVES: This study aims to identify autonomous risk factors for postoperative dysphagia in oral cancer patients and construct a nomogram prediction model to improve risk assessment accuracy and feasibility in clinical settings. METHODS: A prospective cohort study was conducted from March to July 2022 among oral cancer patients undergoing surgical interventions at the Department of Head and Neck Surgery. Clinical data were collected using the Postoperative Dysphagia Risk Factor Questionnaire. Swallowing function was assessed with the Mann Assessment of Swallowing Ability-Oral Cancer (MASA-OC). Lasso regression identified potential predictor variables, followed by univariate and multivariate logistic regression analyses. A predictive model was developed using R Studio 4.1.2 and rigorously evaluated with ROC curves, Hosmer-Lemeshow tests, and calibration curves. Internal validation utilized Bootstrap methodology with 1000 repetitive samples. RESULTS: The cohort included 257 oral cancer patients, with 73.9 % experiencing postoperative dysphagia. Independent predictors included functional status, depressive symptoms, pT stage, surgical techniques, glossoplasty, maxillectomy, and post-surgery nasopharyngeal tube retention. The predictive model achieved an AUC of 0.933, sensitivity of 90.9 %, and specificity of 81.7 %. Hosmer-Lemeshow test (P = 0.715) and C-index (0.934) indicated satisfactory model fit. Internal validation yielded an AUC of 0.912, sensitivity of 93.3 %, and specificity of 63.8 %. Calibration curves demonstrated alignment between predicted and observed outcomes. CONCLUSION: A nomogram integrating recognized risk factors shows promise in predicting postoperative dysphagia in oral cancer patients, enhancing precision and aiding healthcare professionals in risk evaluation and patient care strategies.
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OBJECTIVE: This study aimed to describe the clinical and genetic characteristics of Chinese patients with congenital fibrosis of the extraocular muscles (CFEOM), and to evaluate the phenotype-genotype correlations in these patients. METHODS: This was a retrospective study. Patients with CFEOM underwent detailed ophthalmic examinations and magnetic resonance imaging (MRI). Panel-based next-generation sequencing was performed to identify pathogenic variants of disease-causing genes. RESULTS: Sixty-two patients with CFEOM were recruited into this study. Thirty-nine patients were diagnosed with CFEOM1 and 23 with CFEOM3. Forty-nine of the 62 patients with CFEOM carried either KIF21A (41/49) or TUBB3 variants (8/49). Six known missense variants in the KIF21A and TUBB3 genes, and a novel variant (c.3906T > A, p.D1302E) in the KIF21A gene were detected. Most patients with CFEOM1 carrying the KIF21A mutation displayed isolated CFEOM, whereas patients with CFEOM3 carrying the TUBB3 mutation had a wide range of clinical manifestations, either CFEOM alone or syndromes. Nystagmus was also present in 12 patients with CFEOM. Furthermore, the MRI findings varied, ranging from attenuation of the extraocular muscles to dysgenesis of the cranial nerves and brain structure. CONCLUSIONS: The novel variants identified in this study will further expand the spectrum of pathogenic variants in CFEOM-related genes. However, no phenotype-genotype correlations were established because of the diversity of the clinical characteristics of these patients.
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Fibrose , Cinesinas , Humanos , Masculino , Feminino , Fibrose/genética , Fibrose/patologia , Criança , Cinesinas/genética , Estudos Retrospectivos , Adolescente , Pré-Escolar , Adulto , Tubulina (Proteína)/genética , Adulto Jovem , Imageamento por Ressonância Magnética , Músculos Oculomotores/patologia , Músculos Oculomotores/diagnóstico por imagem , Povo Asiático/genética , Lactente , Mutação/genética , População do Leste Asiático , Transtornos Congênitos de Denervação Craniana , OftalmoplegiaRESUMO
The PAX6 gene plays an important role in ocular development. Mutations of the PAX6 gene may result in a series of ocular abnormalities, including congenital aniridia, anterior segment dysgenesis (ASD), progressive corneal opacification, glaucoma, and hypoplasia of the fovea and optic nerve, leading to reduced visual acuity and even blindness. This study aimed to describe the diversity of clinical features caused by PAX6 pathogenic variants in 45 Han Chinese patients from 23 unrelated families. All patients underwent detailed clinical assessment. Genetic testing was performed to identify pathogenic variations in the PAX6 gene by next-generation sequencing, minigene splicing assay, RT-qPCR, and long-range PCR. Twenty pathogenic variations were detected in the PAX6 gene from 12 pedigrees and 11 sporadic patients, of which 12 were previously reported and 8 were novel. The clinical phenotypes obtained as a result of the PAX6 gene mutations were complicated and vary among patients, even among those who carried the same variants. Genetic testing is helpful for differential diagnosis. Our genetic findings will expand the spectrum of pathogenic variations in the PAX6 gene. PAX6 pathogenic variants not only cause defects in ocular tissues, such as the iris and retina, but also lead to maldevelopment of the whole eye, resulting in microphthalmia.
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Tibeto-Burman (TB) people have endeavored to adapt to the hypoxic, cold, and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period. However, the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people, as well as their interaction mechanism, remain unknown. Here, we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity, admixture history, and differentiated adaptative features of geographically different TB-speaking people. We identify genetic differentiation related to geography and language among TB-speaking people, consistent with their differentiated admixture process with incoming or indigenous ancestral source populations. A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis. We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers. Adaptative signatures associated with the physical pigmentation (EDAR and SLC24A5) and metabolism (ALDH9A1) are identified in Loloish people, which differed from the high-altitude adaptative genetic architecture in Tibetan. TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.
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PURPOSE: To identify TOPORS mutations in patients with retinitis pigmentosa (RP) from our cohort and summarize the genotypes and phenotypes of TOPORS reported previously. METHOD: Probands with RP phenotypes were recruited from our genetic retinopathy screening work. DNA was extracted from the peripheral venous blood, and exome sequencing was performed. We further examined the clinical data and family history in detail in these patients. TOPORS mutations associated with RP were searched and summarized from the previous reports, and the results were combined with the data presented in our study. The mutation spectrum of TOPORS was systematically analyzed, and the phenotypes of truncated mutations and missense mutations were compared and described. RESULT: Mutations in TOPORS were detected in three families, including two novel mutations (c.2017C>T, p.Arg673Cys, c.2371A>T, p.Lys791Term) and a known frameshift mutation (c.2554_2557delGAGA, p. Glu852fsTer13). A comprehensive analysis showed that 64.1% (25/39) of the mutant alleles are truncated mutations, and 34.3% (12/39) are missense mutations. About 89.7% (35/39) of the mutations are located in the terminal half of exon 3, which affected the C-terminal of the TOPORS protein. Night blindness was a common onset symptom, and TOPORS-related ERG changes can be observed in early stage. In addition, patients with missense mutations retained better central vision in older age compared to the patients with truncated mutations. CONCLUSION: We expand the mutation spectrum and assess the possible genotype-phenotype correlations of TOPORS, which can provide a valuable reference for exploring the pathogenesis of adRP caused by TOPORS mutations.
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Proteínas de Neoplasias , Proteínas Nucleares , Retinose Pigmentar , Ubiquitina-Proteína Ligases , Análise Mutacional de DNA , Humanos , Mutação , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Linhagem , Fenótipo , Retinose Pigmentar/genética , Retinose Pigmentar/patologia , Ubiquitina-Proteína Ligases/genéticaRESUMO
Background: This study sought to define different adaptive changes in the molecular levels of the overacting inferior oblique muscle in primary and secondary inferior oblique overaction. Methods: The inferior oblique muscles of patients with congenital superior oblique palsy (SOP) and those of patients with congenital esotropia were collected during surgery. RNA-seq technology was performed to detect the differentially expressed genes (DEGs) between the two groups. A comprehensive analysis of the gene expression profiles was then conducted, including the identification of DEGs, a Gene Ontology (GO) analysis, and a gene set enrichment analysis (GSEA). Finally, a protein-protein interaction (PPI) network was constructed with Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software. Results: We identified 221 DEGs, of which 104 were significantly upregulated and 117 were downregulated in the SOP group. Additionally, several isoforms of the myosin heavy chain (MyHC) gene were found to be significantly and differentially expressed in the SOP group, including 3 upregulated fast-twitch MyHC isoforms (i.e., MYH1, MYH4, and MYH13) and 1 downregulated slow-twitch MyHC isoform (i.e., MYH3). The GO analysis indicated that the upregulated DEGs were mainly enriched in the muscle system process and muscle contraction. The GSEA analysis revealed that the upregulated pathways of ribosome, proteasome, oxidative phosphorylation, fatty acid metabolism, viral myocarditis, and cardiac muscle contraction were enriched. Conclusions: Our findings provide insights into the different molecular changes of inferior oblique muscle overaction secondary to SOP and suggest the potential pathological mechanisms of inferior oblique overaction (IOOA) in SOP. The results suggest that upregulated fast-twitch MyHC isoforms and downregulated slow-twitch MyHC isoform in SOP may contribute to the increased force of its inferior oblique muscle.
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Background: Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare disorder mainly involved in ocular movement and spinal development. It is caused by a roundabout guidance receptor 3 (ROBO3) gene mutation. This study aimed to describe the clinical features of six patients with HGPPS and investigate the corresponding ROBO3 gene mutations. Methods: Patients underwent detailed clinical and imaging examinations. Whole-exome sequencing was performed to detect nucleotide variations in the disease-causing genes of HGPPS. Results: Six pathogenic variants were detected in the ROBO3 gene from six patients with HGPPS, including two novel compound heterozygous mutations, c.1447C > T (p.R483X) and c.2462G > C (p.R821P); c.1033G > C (p.V345L) and c.3287G > T (p.C1096F); a novel homozygous indel mutation, c.565dupC (p.R191Pfs*61); and a known missense mutation, c.416G > T (p.G139V). Patients with HGPPS had horizontal conjugated eye movement defects and scoliosis with variable degrees, as well as flattened pontine tegmentum and uncrossed corticospinal tracts on magnetic resonance imaging. Conclusion: Our genetic findings will expand the spectrum of ROBO3 mutations and help inform future research on the molecular mechanism of HGPPS.
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Mutations in the FERM domain containing 7 (FRMD7) gene have been proven to be responsible for infantile nystagmus (IN). The purpose of this study is to investigate FRMD7 gene mutations in patients with IN, and to evaluate the nystagmus intensity among patients with and without FRMD7 mutations. The affected males were subdivided into three groups according to whether or not having FRMD7 mutations and the types of mutations. Fifty-two mutations were detected in FRMD7 in 56 pedigrees and 34 sporadic patients with IN, including 28 novel and 24 previous reported mutations. The novel identified mutations further expand the spectrum of FRMD7 mutations. The parameters of nystagmus intensity and the patients' best corrected visual acuity were not statistically different among the patients with and without identified FRMD7 mutations, and also not different among patients with different mutant types. The FERM-C domain, whose amino acids are encoded by exons 7, 8 and 9, could be the harbor region for most mutations. Loss-of-function is suggested to be the common molecular mechanism for the X-linked infantile nystagmus.
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Proteínas do Citoesqueleto , Doenças Genéticas Ligadas ao Cromossomo X , Proteínas de Membrana , Nistagmo Congênito , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Masculino , Proteínas de Membrana/genética , Mutação , Nistagmo Congênito/genética , LinhagemRESUMO
It is urgent to solve the contamination of aflatoxin B1 (AFB1) in food and water. In this study, the mesoporous silica was prepared from rice husk, which was then magnetized using the precipitation technique, followed by amino-modification with 3-aminopropyltriethoxysilane, forming amino-grafted magnetic mesoporous silica (NMMS). X-ray diffraction, Fourier transformed infrared spectra, and thermogravimetric analysis showed the successful grafting of amino groups on NMMS with a percentage of grafting up to 13.33%. The NMMS had an adsorption capacity of 169.88 µg/g and a removal rate of 93.43% for AFB1 in aqueous solutions at 20 °C, pH 7.0 for 2.0 h. The adsorption of AFB1 by NMMS followed a quasi-second-order kinetics and fitted well with the Langmuir model. Furthermore, the removal rate of AFB1 by NMMS remained 72.43% after repeating the adsorption-desorption process for five times. This study provided a facile approach to prepare NMMS for effective removal of AFB1.
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Oryza , Poluentes Químicos da Água , Adsorção , Aflatoxina B1 , Cinética , Fenômenos Magnéticos , Dióxido de Silício , ÁguaRESUMO
Edible oils, especially peanut oil, usually contain aflatoxin B1 (AFB1) at extremely high concentrations. This study focused on the synthesis of rice husk-based mesoporous silica (MCM-41) for the removal of AFB1 from peanut oil. MCM-41 was characterized by X-ray diffraction, N2 physisorption, and transmission electron microscope. MCM-41 was shown to have ordered channels with high specific surface area (1246 m2/g), pore volume (1.75 cm3/g), and pore diameter (3.11 nm). Under the optimal concentration of 1.0 mg/mL of the adsorbent dose, the adsorption behavior of MCM-41, natural montmorillonite (MONT), and commercial activated carbon (CA) for AFB1 were compared. The adsorption of AFB1 in peanut oil onto the three adsorbents was slower compared to that of AFB1 in an aqueous solution. In addition, the pseudo-second-order kinetic model better fit the adsorption kinetics of AFB1, while the adsorption mechanism followed the Langmuir adsorption isotherm on the three adsorbents. The calculated maximum adsorbed amounts of AFB1 on MONT, MCM-41, and CA were 199.41, 215.93, and 248.93 ng/mg, respectively. These results suggested that MCM-41 without modification could meet market demand and could be considered a good candidate for the removal of AFB1 from peanut oil. This study provides insights that could prove to be of economic and practical value.
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Aflatoxina B1/química , Oryza , Óleo de Amendoim/química , Dióxido de Silício/química , Adsorção , Contaminação de Alimentos/prevenção & controleRESUMO
The palm print contains a great deal of information which is of great research and application value. This paper provides palm print research methods, application, and the relationship between the palm print and cancer.