Dear Editor,I am Dr.Sabiha Gungor Kobat,from the Department of Ophthalmology,Elazig Health Sciences University,Elazig,Turkey.I am writing to present an exceedingly rare case of two siblings,one of whom developed Biett...Dear Editor,I am Dr.Sabiha Gungor Kobat,from the Department of Ophthalmology,Elazig Health Sciences University,Elazig,Turkey.I am writing to present an exceedingly rare case of two siblings,one of whom developed Bietti crystalline dystrophy(BCD)with choroidal neovascularization at the age of 13 years,and the other has asymptomatic BCD at 8 years old.展开更多
AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy（BCD） and to provide clinical features of these patients. BCD is a rare monogenic autosomal rece...AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy（BCD） and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD.METHODS: Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.RESULTS: Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations（p.F73 L,p.R400H）, two splice site mutations（c.802-8810del17ins GC, c.1091-2A 】G）, and one single base-pair deletion（p.T479 Tfs X7 or c.1437 del C）. The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479 Tfs X7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes.CONCLUSION: Mutation c.802-8810del17ins GC and c.1091-2A】G are common mutations in Chinese patientswith BCD. Our results expand the allelic heterogeneity of BCD.展开更多
PURPOSE: To describe the clinical and genetic characteristics of six Japanese families with Bietti’s crystalline corneoretinal dystrophy (BCD). DESIGN: Case reports and results of DNA analysis. METHODS: Mutation scre...PURPOSE: To describe the clinical and genetic characteristics of six Japanese families with Bietti’s crystalline corneoretinal dystrophy (BCD). DESIGN: Case reports and results of DNA analysis. METHODS: Mutation screening was performed on six unrelated patients with BCD by direct sequencing. The clinical features were characterized by the visual acuity, slit-lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing. RESULTS: An identical IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation in the CYP4V2 gene was identified in five of the patients with BCD; the sixth patient had a novel Trp340X mutation in the CYP4V2 gene. Three patients showed crystalline-like deposits at the limbus by specular microscopy. Ophthalmic findings of all patients had a rapid progression after age 50 years. CONCLUSIONS:Our findings suggest that the IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation is a common mutation in Japanese patients with BCD. Although phenotypic variabilitywas found, the natural course was almost the same in all of our patients.展开更多
Objective We wanted to investigate the radial peripapillary capillary(RPC)network in patients with Bietti crystalline dystrophy(BCD).Methods We compared RPC densities in the disk and different peripapillary regions,ob...Objective We wanted to investigate the radial peripapillary capillary(RPC)network in patients with Bietti crystalline dystrophy(BCD).Methods We compared RPC densities in the disk and different peripapillary regions,obtained using optical coherence tomography angiography in 22 patients with BCD(37 eyes)and 22 healthy subjects(37 eyes).The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging,comparing the RPC densities of the two.Results The disk area RPC density was 38.8%±6.3%in the BCD group and 49.2%±6.1%in the control group(P<0.001),and peripapillary region RPC density was significantly lower in the BCD group than in the control group(49.1%±4.7%and 54.1%±3.0%,respectively,P<0.001).There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups;the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD.Conclusion The BCD group RPC density was significantly lower than the control group.The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD.In contrast,the reduction of RPC density in superior,inferior,and nasal quadrants occurred mainly in Stage 2.展开更多
AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy(BCD) proband in a Chinese family.METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal ...AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy(BCD) proband in a Chinese family.METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal neovascularization(CNV) and her parents underwent complete ophthalmic examinations, including fundus autofluorescence(AF), fundus photography(FP), fundus fluorescein angiography(FFA), visual field testing, full-field electroretinography(ERG), optical coherence tomography(OCT) and optical coherence tomography angiography(OCTA). The sequencing of the CYP4 V2 gene was performed to the whole family.RESULTS: Bilateral tiny glittering crystal-like deposits and differing extent of atrophy of the retinal pigment epithelium(RPE) were found in the posterior pole of her fundus. The diffuse hypo-fluorescence shown on AF images and window defects shown on FFA both indicated the atrophy of the RPE and choriocapillaris. OCT showed the thinning of the RPE and choriocapillaris layer, ellipsoid zone(EZ) band defect and CNV in both eyes. OCTA images proofed bilateral type 2 CNV. The visual field test showed central and paracentral scotoma. ERG showed a slightly decreased b-wave in scotopic ERG. Gene sequencing identified three mutations of the CYP4 V2 gene, c.802_807 del, c.810 del T, and c.1388 G>A. The mutation c.1388 G>A was a novel substitution mutation.CONCLUSION: The novel mutation c.1388 G>A may be a possible cause that could induce the clinical phenotype of BCD.展开更多
Prpose: To observe different features of indocyanine green angiography(ICGA) andtifocal electroretinography (ERG) in the diffuse and regional type of Bieti′sc stalline retinopathy (BCR). Thods: ICGA and the multifoca...Prpose: To observe different features of indocyanine green angiography(ICGA) andtifocal electroretinography (ERG) in the diffuse and regional type of Bieti′sc stalline retinopathy (BCR). Thods: ICGA and the multifocal ERG were performed in two cases of the diffuse andregional type of BCR respectively. These data were compared with fluoresceinangiography (FA), standard Ganzfeld ERG, and visual field testing. Results: In the regional case, ICGA revealed reduced perfusion of the choroidalcirculation in the early phase and multiple hypofluorescent spots in the posterior pole in the late phase, due to choriocapillaris filling defect; the extent of choroiocapillaris losswas shown in early phase of ICGA and there were multifocal hyperfluorescent dotssurrounding hypofluorescent spots in late phase in the diffuse case. The multifocal ERGshowed that the central responses were markedly depressed, corresponding to the visualfield defects, while the findings of Ganzfeld ERG were normal in the regional BCR;however, both the multifocal ERG and Ganzfeld ERG were severely subnormal in thediffuse case.Conclusions: The features of ICGA and multifocal ERG are different between the diffuseand regional BCR. In the meantime, the two tools are also useful to differentiate the typeand assess the extentof evolution in BCR.展开更多
BACKGROUND Many genetic and metabolic diseases affect the liver,but diagnosis can be difficult because these diseases may have complex clinical manifestations and diverse clinical patterns.There is also incomplete cli...BACKGROUND Many genetic and metabolic diseases affect the liver,but diagnosis can be difficult because these diseases may have complex clinical manifestations and diverse clinical patterns.There is also incomplete clinical knowledge of these many different diseases and limitations of current testing methods.CASE SUMMARY We report a 53-year-old female from a rural area in China who was hospitalized for lower limb edema,abdominal distension,cirrhosis,and hypothyroidism.We excluded the common causes of liver disease(drinking alcohol,using traditional Chinese medicines,hepatitis virus infection,autoimmunity,and hepatolenticular degeneration).When she was 23-years-old,she developed night-blindness that worsened to complete blindness,with no obvious cause.Her parents were first cousins,and both were alive.Analysis of the patient’s family history indicated that all 5 siblings had night blindness and impaired vision;one sister was completely blind;and another sister had night-blindness complicated with cirrhosis and subclinical hypothyroidism.Entire exome sequencing showed that the patient,parents,and siblings all had mutations in the cytochrome P450 4V2gene(CYP4V2).The CYP4V2 mutations of the parents and two sisters were heterozygous,and the others were homozygous.Two siblings also had heterozygous dual oxidase activator 2(DUOXA2) mutations.CONCLUSION Mutations in the CYP4V2 gene may affect lipid metabolism and lead to chronic liver injury,fibrosis,and cirrhosis.展开更多
文摘Dear Editor,I am Dr.Sabiha Gungor Kobat,from the Department of Ophthalmology,Elazig Health Sciences University,Elazig,Turkey.I am writing to present an exceedingly rare case of two siblings,one of whom developed Bietti crystalline dystrophy(BCD)with choroidal neovascularization at the age of 13 years,and the other has asymptomatic BCD at 8 years old.
文摘AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy（BCD） and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD.METHODS: Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms.RESULTS: Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations（p.F73 L,p.R400H）, two splice site mutations（c.802-8810del17ins GC, c.1091-2A 】G）, and one single base-pair deletion（p.T479 Tfs X7 or c.1437 del C）. The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479 Tfs X7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes.CONCLUSION: Mutation c.802-8810del17ins GC and c.1091-2A】G are common mutations in Chinese patientswith BCD. Our results expand the allelic heterogeneity of BCD.
文摘PURPOSE: To describe the clinical and genetic characteristics of six Japanese families with Bietti’s crystalline corneoretinal dystrophy (BCD). DESIGN: Case reports and results of DNA analysis. METHODS: Mutation screening was performed on six unrelated patients with BCD by direct sequencing. The clinical features were characterized by the visual acuity, slit-lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing. RESULTS: An identical IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation in the CYP4V2 gene was identified in five of the patients with BCD; the sixth patient had a novel Trp340X mutation in the CYP4V2 gene. Three patients showed crystalline-like deposits at the limbus by specular microscopy. Ophthalmic findings of all patients had a rapid progression after age 50 years. CONCLUSIONS:Our findings suggest that the IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation is a common mutation in Japanese patients with BCD. Although phenotypic variabilitywas found, the natural course was almost the same in all of our patients.
文摘Objective We wanted to investigate the radial peripapillary capillary(RPC)network in patients with Bietti crystalline dystrophy(BCD).Methods We compared RPC densities in the disk and different peripapillary regions,obtained using optical coherence tomography angiography in 22 patients with BCD(37 eyes)and 22 healthy subjects(37 eyes).The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging,comparing the RPC densities of the two.Results The disk area RPC density was 38.8%±6.3%in the BCD group and 49.2%±6.1%in the control group(P<0.001),and peripapillary region RPC density was significantly lower in the BCD group than in the control group(49.1%±4.7%and 54.1%±3.0%,respectively,P<0.001).There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups;the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD.Conclusion The BCD group RPC density was significantly lower than the control group.The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD.In contrast,the reduction of RPC density in superior,inferior,and nasal quadrants occurred mainly in Stage 2.
基金Supported by National Key R&D Program of China(No.2020YFC2008200)Capital Clinical Diagnosis and Treatment Technology Research and Demonstration Application Project of China(No.Z191100006619029)。
文摘AIM: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy(BCD) proband in a Chinese family.METHODS: A Chinese female diagnosed with BCD complicated by bilateral choroidal neovascularization(CNV) and her parents underwent complete ophthalmic examinations, including fundus autofluorescence(AF), fundus photography(FP), fundus fluorescein angiography(FFA), visual field testing, full-field electroretinography(ERG), optical coherence tomography(OCT) and optical coherence tomography angiography(OCTA). The sequencing of the CYP4 V2 gene was performed to the whole family.RESULTS: Bilateral tiny glittering crystal-like deposits and differing extent of atrophy of the retinal pigment epithelium(RPE) were found in the posterior pole of her fundus. The diffuse hypo-fluorescence shown on AF images and window defects shown on FFA both indicated the atrophy of the RPE and choriocapillaris. OCT showed the thinning of the RPE and choriocapillaris layer, ellipsoid zone(EZ) band defect and CNV in both eyes. OCTA images proofed bilateral type 2 CNV. The visual field test showed central and paracentral scotoma. ERG showed a slightly decreased b-wave in scotopic ERG. Gene sequencing identified three mutations of the CYP4 V2 gene, c.802_807 del, c.810 del T, and c.1388 G>A. The mutation c.1388 G>A was a novel substitution mutation.CONCLUSION: The novel mutation c.1388 G>A may be a possible cause that could induce the clinical phenotype of BCD.
文摘Prpose: To observe different features of indocyanine green angiography(ICGA) andtifocal electroretinography (ERG) in the diffuse and regional type of Bieti′sc stalline retinopathy (BCR). Thods: ICGA and the multifocal ERG were performed in two cases of the diffuse andregional type of BCR respectively. These data were compared with fluoresceinangiography (FA), standard Ganzfeld ERG, and visual field testing. Results: In the regional case, ICGA revealed reduced perfusion of the choroidalcirculation in the early phase and multiple hypofluorescent spots in the posterior pole in the late phase, due to choriocapillaris filling defect; the extent of choroiocapillaris losswas shown in early phase of ICGA and there were multifocal hyperfluorescent dotssurrounding hypofluorescent spots in late phase in the diffuse case. The multifocal ERGshowed that the central responses were markedly depressed, corresponding to the visualfield defects, while the findings of Ganzfeld ERG were normal in the regional BCR;however, both the multifocal ERG and Ganzfeld ERG were severely subnormal in thediffuse case.Conclusions: The features of ICGA and multifocal ERG are different between the diffuseand regional BCR. In the meantime, the two tools are also useful to differentiate the typeand assess the extentof evolution in BCR.
基金Supported by the National Natural Science Foundation of China,No.82160370the Science and Technology Planning Projects of Guizhou Province and Zunyi City,No.QKHJC-ZK[2022]YB642,No.ZSKH·HZ(2022)344,No.gzwjkj2020-1-041,and No.ZMC·YZ[2018]38。
文摘BACKGROUND Many genetic and metabolic diseases affect the liver,but diagnosis can be difficult because these diseases may have complex clinical manifestations and diverse clinical patterns.There is also incomplete clinical knowledge of these many different diseases and limitations of current testing methods.CASE SUMMARY We report a 53-year-old female from a rural area in China who was hospitalized for lower limb edema,abdominal distension,cirrhosis,and hypothyroidism.We excluded the common causes of liver disease(drinking alcohol,using traditional Chinese medicines,hepatitis virus infection,autoimmunity,and hepatolenticular degeneration).When she was 23-years-old,she developed night-blindness that worsened to complete blindness,with no obvious cause.Her parents were first cousins,and both were alive.Analysis of the patient’s family history indicated that all 5 siblings had night blindness and impaired vision;one sister was completely blind;and another sister had night-blindness complicated with cirrhosis and subclinical hypothyroidism.Entire exome sequencing showed that the patient,parents,and siblings all had mutations in the cytochrome P450 4V2gene(CYP4V2).The CYP4V2 mutations of the parents and two sisters were heterozygous,and the others were homozygous.Two siblings also had heterozygous dual oxidase activator 2(DUOXA2) mutations.CONCLUSION Mutations in the CYP4V2 gene may affect lipid metabolism and lead to chronic liver injury,fibrosis,and cirrhosis.
