AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen fo...AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen for pathogenic genes and candidate pathogenic variants were obtained by bioinformatics analysis.Sanger sequencing was used for validation and familial cosegregation analysis to determine pathogenic variants.Pymol software was applied to produce a 3D structure image of the protein to analyze the structural and functional alterations of the protein.The pathogenicity of genetic variants was evaluated according to ACMG guidelines.RESULTS:The chief clinical symptoms of this proband included obvious visual impairment,protanopia and deuteranopia,peripheral punctate pigment,arteriolar attenuation,structural and functional abnormalities revealed by optical coherence tomography(OCT)and electroretinography(ERG)including thinning of the outer retinal layer,a discontinuous external limiting membrane(ELM)and ellipsoid zone(EZ),granular hyperreflective projections between the retinal pigment epithelium and the interdigitation zone,severe attenuation of photopic responses with mild reduced scotopic responses.Wholeexome sequencing revealed that the proband carried a heterozygous variant of the GUCY2D gene:c.2512C>T:p.Arg838Cys.Three-dimensional molecular structure analysis of the protein revealed that amino acid 838 was mutated from polar positively charged arginine to polar uncharged cysteine,and the spatial structure of the protein changed greatly.Sanger sequencing co-segregation analysis confirmed that such a variant was detected in neither the phenotypically normal parents nor the daughter of the proband,which was presumed to be a de novo one.The variant was determined to be pathogenic according to ACMG guidelines.The heterozygous variant at the same site was detected in the abnormal proband’s son with moderate attenuation of photopic electroretinographic responses and normal scotopic electroretinographic responses,supporting autosomal dominant inheritance.CONCLUSION:The de novo variant causing atypical autosomal dominant CRD is identified in a Chinese consanguineous family and this variant passes through this family in an autosomal dominant mode of inheritance,revealing the complex diversity and unpredictability of the inheritance mode for common single-gene genetic disease.展开更多
This paper presents a solution to tracking control problem for a class of nonlinear systems with unknown parameters ana uncertain time-varying delays. A new adaptive neural network （NN） dynamic surface controller （...This paper presents a solution to tracking control problem for a class of nonlinear systems with unknown parameters ana uncertain time-varying delays. A new adaptive neural network （NN） dynamic surface controller （DSC） is developed. Some assumptions on uncertain time delays, which were required to be satisfied in previous works, are removed by introducing a novel indirect neural network algorithm into dynamic surface control framework. Also, the designed controller is independent of the time delays. Moreover, the dynamic compensation terms are introduced to facilitate the controller design. It is shown that the closed-loop tracking error converges to a small neighborhood of zero. Finally, a chaotic circuit system is initially bench tested to show the effectiveness of the proposed method.展开更多
This paper presents an up-to-date study on the observer-based control problem for nonlinear systems in the presence of unmodeled dynamics and actuator dead-zone.By introducing a dynamic signal to dominate the unmodele...This paper presents an up-to-date study on the observer-based control problem for nonlinear systems in the presence of unmodeled dynamics and actuator dead-zone.By introducing a dynamic signal to dominate the unmodeled dynamics and using an adaptive nonlinear damping to counter the effects of the nonlinearities and dead-zone input,the proposed observer and controller can ensure that the closed-loop system is asymptotically stable in the sense of uniform ultimate boundedness.Only one adaptive parameter is needed no matter how many unknown parameters there are.The system investigated is more general and there is no need to solve Linear matrix inequality （LMI）.Moreover,with our method,some assumptions imposed on nonlinear terms and dead-zone input are relaxed.Finally,simulations illustrate the effectiveness of the proposed adaptive control scheme.展开更多
基金Supported by the National Natural Science Foundation of China(No.82260206)Natural Science Foundation of Ningxia(No.2022AAC03387)+1 种基金Major Achievement Transformation Project of Ningxia Hui Autonomous Region(No.2022CJE09011)the Key Research Development Project of Ningxia Hui Autonomous Region(No.2024BEG02017).
文摘AIM:To analyze the pathogenicity and clinical features of patients in a consanguineous cone-rod dystrophy(CRD)family due to heterozygous variants in the GUCY2D gene.METHODS:Whole exome sequencing was used to screen for pathogenic genes and candidate pathogenic variants were obtained by bioinformatics analysis.Sanger sequencing was used for validation and familial cosegregation analysis to determine pathogenic variants.Pymol software was applied to produce a 3D structure image of the protein to analyze the structural and functional alterations of the protein.The pathogenicity of genetic variants was evaluated according to ACMG guidelines.RESULTS:The chief clinical symptoms of this proband included obvious visual impairment,protanopia and deuteranopia,peripheral punctate pigment,arteriolar attenuation,structural and functional abnormalities revealed by optical coherence tomography(OCT)and electroretinography(ERG)including thinning of the outer retinal layer,a discontinuous external limiting membrane(ELM)and ellipsoid zone(EZ),granular hyperreflective projections between the retinal pigment epithelium and the interdigitation zone,severe attenuation of photopic responses with mild reduced scotopic responses.Wholeexome sequencing revealed that the proband carried a heterozygous variant of the GUCY2D gene:c.2512C>T:p.Arg838Cys.Three-dimensional molecular structure analysis of the protein revealed that amino acid 838 was mutated from polar positively charged arginine to polar uncharged cysteine,and the spatial structure of the protein changed greatly.Sanger sequencing co-segregation analysis confirmed that such a variant was detected in neither the phenotypically normal parents nor the daughter of the proband,which was presumed to be a de novo one.The variant was determined to be pathogenic according to ACMG guidelines.The heterozygous variant at the same site was detected in the abnormal proband’s son with moderate attenuation of photopic electroretinographic responses and normal scotopic electroretinographic responses,supporting autosomal dominant inheritance.CONCLUSION:The de novo variant causing atypical autosomal dominant CRD is identified in a Chinese consanguineous family and this variant passes through this family in an autosomal dominant mode of inheritance,revealing the complex diversity and unpredictability of the inheritance mode for common single-gene genetic disease.
基金supported by Natural Science Foundation of Hebe Province(No.F2014208119)Doctoral Foundation of Hebei University of Science and Technology(No.010075)
文摘This paper presents a solution to tracking control problem for a class of nonlinear systems with unknown parameters ana uncertain time-varying delays. A new adaptive neural network （NN） dynamic surface controller （DSC） is developed. Some assumptions on uncertain time delays, which were required to be satisfied in previous works, are removed by introducing a novel indirect neural network algorithm into dynamic surface control framework. Also, the designed controller is independent of the time delays. Moreover, the dynamic compensation terms are introduced to facilitate the controller design. It is shown that the closed-loop tracking error converges to a small neighborhood of zero. Finally, a chaotic circuit system is initially bench tested to show the effectiveness of the proposed method.
基金supported by National Natural Science Foundation of China (No. 60704009)
文摘This paper presents an up-to-date study on the observer-based control problem for nonlinear systems in the presence of unmodeled dynamics and actuator dead-zone.By introducing a dynamic signal to dominate the unmodeled dynamics and using an adaptive nonlinear damping to counter the effects of the nonlinearities and dead-zone input,the proposed observer and controller can ensure that the closed-loop system is asymptotically stable in the sense of uniform ultimate boundedness.Only one adaptive parameter is needed no matter how many unknown parameters there are.The system investigated is more general and there is no need to solve Linear matrix inequality （LMI）.Moreover,with our method,some assumptions imposed on nonlinear terms and dead-zone input are relaxed.Finally,simulations illustrate the effectiveness of the proposed adaptive control scheme.
