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
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
In this cross-sectional observational study,we conducted comprehensive ophthalmic evaluations,including fundus imaging,fundus autofluorescence(FAF),swept-source optical coherence tomography(SS-OCT),microperimetry,and ...In this cross-sectional observational study,we conducted comprehensive ophthalmic evaluations,including fundus imaging,fundus autofluorescence(FAF),swept-source optical coherence tomography(SS-OCT),microperimetry,and electroretinography,in 164 patients with Bietti crystalline dystrophy(BCD)from 159 families.The mean age of onset was(29.9±8.9)years,with night blindness being the most common onset symptom(54.3%).FAF revealed diffuse hypoautofluorescence in 86.7%of eyes,and SS-OCT identified outer retinal tubulations(ORTs)in 69.9%of eyes,indicative of severe retinal pigment epithelium(RPE)dysfunction.Microperimetry demonstrated a gradual decline in retinal sensitivity and fixation stability with disease progression,particularly in advanced stages.We identified 34 distinct CYP4V2 variants,three of which were novel.Patients with biallelic truncating mutations experienced earlier disease onset and progressed to legal blindness at a younger age.These findings provide a comprehensive overview of structural and functional deterioration in BCD and underscore the significant impact of truncating mutations on disease progression.展开更多
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.
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.
基金supported by the National Natural Science Foundation of China(82220108017,82141128)the Capital Health Research and Development of Special(2024-1-2052)+1 种基金Science&Technology Project of Beijing Municipal Science&Technology Commission(Z201100005520045)Sanming Project of Medicine in Shenzhen(SZSM202311018)。
文摘In this cross-sectional observational study,we conducted comprehensive ophthalmic evaluations,including fundus imaging,fundus autofluorescence(FAF),swept-source optical coherence tomography(SS-OCT),microperimetry,and electroretinography,in 164 patients with Bietti crystalline dystrophy(BCD)from 159 families.The mean age of onset was(29.9±8.9)years,with night blindness being the most common onset symptom(54.3%).FAF revealed diffuse hypoautofluorescence in 86.7%of eyes,and SS-OCT identified outer retinal tubulations(ORTs)in 69.9%of eyes,indicative of severe retinal pigment epithelium(RPE)dysfunction.Microperimetry demonstrated a gradual decline in retinal sensitivity and fixation stability with disease progression,particularly in advanced stages.We identified 34 distinct CYP4V2 variants,three of which were novel.Patients with biallelic truncating mutations experienced earlier disease onset and progressed to legal blindness at a younger age.These findings provide a comprehensive overview of structural and functional deterioration in BCD and underscore the significant impact of truncating mutations on disease progression.
