AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract ...AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.展开更多
AIM： To identify the mutations of MYOC, OPTN, CYPIB1 and WDR36 in a large Chinese family affected by juvenile open angle glaucoma （JOAG）. METHODS： Of 114 members of one family were recruited in this study. Blood ...AIM： To identify the mutations of MYOC, OPTN, CYPIB1 and WDR36 in a large Chinese family affected by juvenile open angle glaucoma （JOAG）. METHODS： Of 114 members of one family were recruited in this study. Blood samples from twelve members of this pedigree were collected for further research. As a control, 100 unrelated subjects were recruited from the same hospital. The exon and flanking intron sequences of candidate genes were amplified using the polymerase chain reaction and direct DNA sequencing. RESULTS： The proband （111：10） was a seventy-three years old woman with binocular JOAG at the age of 31. A recurrent heterozygous mutation （c.1099G〉A） of MYOC was identified in the three JOAG patients and another suspect. This transition was located in the first base pair of codon 367 （GGA〉AGA） in exon 3 of MYOC and was predicted to be a missense substitution of glycine to arginine （p.G367R） in myocilin. Mutations in OPTN, CYPIB1 or WDR36 were not detected in this study. The G367R mutation was not present in unaffected family members or in 100 ethnically matched controls. Other variants of the coding regions of candidate genes were not detected in all participants. To date, this family was the largest to have been identified as carrying a certain MYOC mutation in China, further evidence of a founder effect for the G367R MYOC mutant was provided by our data. CONCLUSION： A MYOC c.1099G〉A mutation in an autosomal dominant JOAG family is identified and the characteristic phenotypes among the patients are summarized. Genetic testing could be utilized in high-risk populations and be helpful not only for genetic counseling, but also for early diagnosis and treatment of affected patients or carriers of inherited JOAG.展开更多
AIM:To evaluate the feasibility of promoting genetic detection for granular corneal dystrophy type 2(GCD2)by a questionnaire conducted among citizens in five cities in China.METHODS:The data were collected by question...AIM:To evaluate the feasibility of promoting genetic detection for granular corneal dystrophy type 2(GCD2)by a questionnaire conducted among citizens in five cities in China.METHODS:The data were collected by questionnaire,and analyzed by Chi-square test and one-tailed t test in IBM SPSS statistics.RESULTS:Based on the survey data on the awareness of GCD2 genetic detection in this study and the positive predictive analysis report of the citizens in five cities in China,the vast majority(84.2%)of respondents had never heard of it and did not know that GCD2 patients have been prohibited from performing excimer surgery that can deteriorate GCD2 patients’condition even leading to blindness.Though 3.4%of patients understood GCD2 very much,they have no idea that GCD2 could not be 100%accuracy diagnosed by the conventional inspection methods.CONCLUSION:It is feasible and necessary to use GCD2 genetic detection as an excimer preoperative examination project.In order to promote the development of detection project,a few improvements should be carried out in terms of the promoting efforts,costs,and research progress.展开更多
基金Supported by the Natural Science Foundation of Fujian Province(No.2021J01229)National Key Research and Development Program of China(No.2016YFC1000307).
文摘AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.
基金Supported by Natural Science Foundation of China(No.81270999No.81570870)Professor Academic Development Fund of Fujian Medical University(No.JS14019)
文摘AIM： To identify the mutations of MYOC, OPTN, CYPIB1 and WDR36 in a large Chinese family affected by juvenile open angle glaucoma （JOAG）. METHODS： Of 114 members of one family were recruited in this study. Blood samples from twelve members of this pedigree were collected for further research. As a control, 100 unrelated subjects were recruited from the same hospital. The exon and flanking intron sequences of candidate genes were amplified using the polymerase chain reaction and direct DNA sequencing. RESULTS： The proband （111：10） was a seventy-three years old woman with binocular JOAG at the age of 31. A recurrent heterozygous mutation （c.1099G〉A） of MYOC was identified in the three JOAG patients and another suspect. This transition was located in the first base pair of codon 367 （GGA〉AGA） in exon 3 of MYOC and was predicted to be a missense substitution of glycine to arginine （p.G367R） in myocilin. Mutations in OPTN, CYPIB1 or WDR36 were not detected in this study. The G367R mutation was not present in unaffected family members or in 100 ethnically matched controls. Other variants of the coding regions of candidate genes were not detected in all participants. To date, this family was the largest to have been identified as carrying a certain MYOC mutation in China, further evidence of a founder effect for the G367R MYOC mutant was provided by our data. CONCLUSION： A MYOC c.1099G〉A mutation in an autosomal dominant JOAG family is identified and the characteristic phenotypes among the patients are summarized. Genetic testing could be utilized in high-risk populations and be helpful not only for genetic counseling, but also for early diagnosis and treatment of affected patients or carriers of inherited JOAG.
基金Supported by National Natural Science Foundation of China(No.81570870)Natural Science Foundation of Fujian Province(No.2016J01375)Innovation and Entrepreneurship Training Program of Fujian Medical University(No.C4015,No.C19067,No.S202010392022X)。
文摘AIM:To evaluate the feasibility of promoting genetic detection for granular corneal dystrophy type 2(GCD2)by a questionnaire conducted among citizens in five cities in China.METHODS:The data were collected by questionnaire,and analyzed by Chi-square test and one-tailed t test in IBM SPSS statistics.RESULTS:Based on the survey data on the awareness of GCD2 genetic detection in this study and the positive predictive analysis report of the citizens in five cities in China,the vast majority(84.2%)of respondents had never heard of it and did not know that GCD2 patients have been prohibited from performing excimer surgery that can deteriorate GCD2 patients’condition even leading to blindness.Though 3.4%of patients understood GCD2 very much,they have no idea that GCD2 could not be 100%accuracy diagnosed by the conventional inspection methods.CONCLUSION:It is feasible and necessary to use GCD2 genetic detection as an excimer preoperative examination project.In order to promote the development of detection project,a few improvements should be carried out in terms of the promoting efforts,costs,and research progress.
