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Purpose: The aim of this study was to elucidate the type of low vision devices (LVDs) prescribed for patients with cone dystrophy, cone–rod dystrophy, and rod–cone dystrophy and to analyze the visual improvement with the devices. Methods: A retrospective review of 300 electronic medical records of patients with cone dystrophy, cone–rod dystrophy, and rod–cone dystrophy referred to the low vision care (LVC) clinic for the first time between 2014 and 2016 at a tertiary eye care center was done. Collected data included the demographic profile of patients, details of LVDs, and best?corrected vision. Results: Out of 300 patients, 62.6% (n = 188) were male and 37.3% (n = 112) were female. Of the cases, 50% (n = 150) had cone–rod dystrophy, 45% (n = 135) had cone dystrophy, and 5% (n = 15) had rod–cone dystrophy. The most commonly prescribed LVD was SEE?TV binocular telescope (n = 6, 2.0%) for distance and dome magnifier (n = 60, 20%) for near. ET?40 dark grey tint (20.6%) was preferred for managing photophobia. There was a statistically significant difference in both distance and near visual acuities with LVDs (P < 0.05) in all categories, except rod–cone dystrophy. Conclusion: Early diagnosis with appropriate prescription of LVDs including tints helps in achieving good quality of vision in patients with cone?related dystrophies.
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Objective:To observe and analyze the ocular clinical features and pathogenic genes of Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. From October 2020 to July 2022, 3 patients and 5 normal family members from 2 families affected with ALMS who visited in the Ophthalmology Department of Henan Children's Hospital were enrolled in the study. These 2 families were without blood relationship. The medical history and family history were inquired. Best corrected visual acuity (BCVA), fundus color photography, full-field electroretinogram (ERG), frequency domain optical coherence tomography (OCT) and systemic examination were performed. 3 ml peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. The second generation sequencing analysis was performed on these members. The suspected pathogenic mutation sites were verified by Sanger, and the pathogenicity of the gene mutation sites were determined by bioinformatics analysis.Results:Three patients from two families all developed nystagmus and photophobia in infancy. In the family 1, the BCVA of both eyes of the proband was no light perception. The fundus examination revealed vascular attenuation and retinal pigment abnormality. OCT showed retinal thinning, loss of photoreceptor layer and atrophy of the retinal pigment epithelium layer. ERG examination showed extinguished. The BCVA of the proband’s younger brother was 0.04 in the right eye and 0.02 in the left eye. The fundus examination revealed vascular attenuation but the pigment distribution was roughly normal. OCT showed blurred photoreceptor layers in both eyes. ERG examination showed extinguished. Two patients developed sensorineural deafness, obesity, acanthosis nigricans, insulin resistance/diabetes, and abnormal liver function. In addition, the proband also had left heart enlargement, hyperlipidemia and abnormal kidney function. The results of genetic testing showed that the proband and his younger brother had compound heterozygous mutations in exon 8 (c.1894C>T/p.Gln632*, M1) and exon 10 (c.9148_9149delCT/p.Leu 3050 Leufs*9, M2) of ALMS1, which were both known mutations. The father of the proband was a carrier of M1 and the mother of the proband was a carrier of M2. The proband of the family 2 had a normal fundus at 23 months old. The amplitude of ERG b wave under the stimulation of the dark adaptation 0.01 and a, b wave under the stimulation of dark adaptation 0.3 were all mild reduced. The amplitude of ERG a, b wave under the stimulation of the light adaptation 0.3 was severity decreased. At 4 years old, the BCVA was 0.01 in the right eye and 0.05 in the left eye. The fundus examination revealed vascular attenuation and bilateral blunted foveal reflex. In addition to severely diminished of a, b wave under the stimulation of dark adaptation 0.3, the rest showed extinguished. There were no systemic abnormalities. The results of genetic testing showed that the proband had compound heterozygous mutations in exon 11 (c.9627delT/p.Pro3210Glnfs*22, M3) and exon 5 (c.1089delT/p.Asp364Ilefs*13, M4) of ALMS1, which were both novel mutations. The father of the proband was a carrier of M3 and the mother of the proband was a carrier of M4. Conclusions:Nystagmus and photophobia are often the first clinical manifestations of ALMS. In the early stage, the fundus can be basically normal. As the disease progresses, the fundus examination reveals vascular attenuation and retinal pigment abnormality, and the reflection of the fovea is unclear. OCT shows the photoreceptor cell layers are blurred or even lost. The final ERG is extinguished. M1, M2, and M3, M4 compound heterozygous mutations may be the pathogeny for family 1 and family 2, respectively.
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Objective:To observe and analyze the gene mutation and clinical phenotype of patients with cone and rod dystrophy (CORD).Methods:A pedigree investigarion. Two CORD pedigrees including 2 patients and 6 family members were enrolled in Ningxia Eye Hospital of People' Hospital of Ningxia Hui Automous Region for this study. The patients were from 2 unrelated families, all of whom were probands. Take medical history with best-corrected visual acuity (BCVA), color vision, slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, optical coherence tomography (OCT), autofluorescence (AF), fluorescein fundus angiography (FFA), electroretinogram (ERG). The peripheral venous blood of patients and their parents was collected, whole genome DNA was extracted, Trio whole genome exome sequencing was performed, Sanger verification and pedigree co-segregation were performed for suspected pathogenic mutation sites. According to the law of inheritance, family history was analyzed to establish its genetic type. Mutational loci pathogenicity was analyzed according to the American College of Medical Genetics (ACMG) guidelines and 4 online tools.Results:Two CORD families showed autosomal recessive inheritance. The proband of pedigree 1 was female, 49 years old. Binocular vision loss with photophobia lasted for 9 years and night blindness for 4 years. The BCVA of right eye and left eye were 0.03 and 0.06, respectively. The results of ERG showed that the amplitudes of dark adaptation 0.01 b-wave and dark adaptation 3.0 a-wave and b-wave in both eyes were slightly decreased, and the amplitudes of light adaptation 3.0 a-wave and b-wave were severely decreased. The proband of pedigree 2 was male, 30 years old. Vision loss in both eyes for 4 years. Denying a history of night blindness. The BCVA of right eye and left eye were 0.3 and 0.2, respectively. The results of ERG showed that the amplitudes of dark adaptation 0.01 b-wave and dark adaptation 3.0 a-wave and b-wave in both eyes were slightly decreased, and the amplitudes of light adaptation 3.0 a-wave and b-wave were severely decreased. The color of optic disc in both eyes was light red, the macular area was atrophic, the foveal reflection disappeared, and the peripheral retina was punctate pigmentation. The main fundus changes in 2 patients were macular atrophy. The proband of pedigree 1 carried compound heterozygous variations c.439-2A>G (M1) and c.676delT (p.F226fs) (M2) on CDHR1 gene. Her father and mother carried M2 and M1 heterozygous mutations, respectively. The proband of pedigree 2 carried compound heterozygous variations c.2665dupC (p.L889fs) (M3) and c.878T>C (p.L293P) (M4) on C2orf71 gene. His father and mother carried M4 and M3 heterozygous mutations, respectively. According to ACMG guidelines and on line tools, 4 variations were considered as pathogenic level. Conclusions:M1 and M2 of CDHR1 gene and M3 and M4 of C2orf71 gene are new pathogenic mutations of CORD. All patients presented with the clinical phenotype of decreased visual acuity and macular atrophy.
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Objective:The clinical phenotypes and pathogenicity of isolated cone-rod dystrophy (CORD) caused by two novel complex heterozygous variants of the CEP290 gene were analyzed using high-resolution multi-mode imaging and gene detection techniques. Methods:A retrospective study. Two patients and two family members from a CORD family who were diagnosed by genetic testing at Henan Provincial People's Hospital in December 2021 were included in the study. All subjects underwent best-corrected visual acuity (BCVA), color fundus photography, autofluorescence, swept-source optical coherence tomography (SS-OCT), adaptive optics fundus imaging, static threshold field, full field and multiple electroretinogram (ERG) examination, as well as other systemic examinations throughout the body. The peripheral venous blood of the subjects was collected, and the whole genome DNA was extracted. DNA sequencing was performed using the Inherited Retinal Disease Kit PS400, and Sanger verification and pedigree co-segregation analysis were performed on the suspected pathogenic mutation sites. Validation was performed by Sanger sequencing, pathogenicity analysis was performed in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. Conservation of variation among different species was analyzed by GERP++, Clustal Omega and Weblogo.Results:Both patients were male, and their ages were 21 and 29 years old, respectively. The right eye and left eye about BCVAs were 0.7, 0.4 and 0.3, 0.4, respectively. The full field and multiple electroretinogram ERG showed a decreased function of cones and rods, especially cones. SS-OCT showed thinning of the outer nuclear layer of macular, and attenuation of ellipsoid zone reflectivity in B-scan. Adaptive optics fundus imaging examination showed that the arrangement of cone cells in the fovea of the fovea was disordered and the density decreased, and the retinal pigment epithelial cells were seen through the atrophy of cone cells in some areas at 10°visual angle. No obvious abnormality was found in other systemic examinations of the whole body. Genetic testing showed that 2 novel compound heterozygous variants c.950T >A (p.Leu317*) (M1) and c.4144_4149del (p.Tyr1382_Glu1383del) (M2) in CEP290 were found in two patients. The first variant was predicted to be harmful in MutationTaster and CADD. GERP++ showed highly conserved among different species. The pathogenicity of the variant was suspected to be likely pathogenic according to ACMG guidelines. The pathogenicity of the second variant was uncertain significance. The parents of the proband had no similar ocular abnormalities. Verified by Sanger sequencing, it was consistent with co-separation in the family. Conclusions:Patients with pure CORD caused by CEP290 gene mutation still retain better vision when the cone structure is abnormal, the density is decreased, and the function of cone and rod cells is decreased. CEP290 M1 and M2 are newly discovered nonsense mutations and newly discovered deletion mutations, which expanded the causative gene spectrum of pure CORD.
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@#AIM: To analyze the gene mutation spectrum of autosomal recessive retinitis pigmentosa(ARRP)pedigrees and cone-rod dystrophy(CORD)pedigrees in Ningxia region of China. <p>METHODS:Totally 35 ARRP pedigrees and 18 CORD pedigrees were included in Ningxia Eye Hospital from September 2016 to February 2020. Peripheral venous blood samples of the proband were collected for targeted capture enrichment and high-throughput sequencing using a genetic retinal disease capture chip that contain 232 pathogenic genes. Online analysis software was used to predict the pathogenicity of suspicious gene variation, and Sanger sequencing was used to analyze the co-segregation of the family members. <p>RESULTS: Totally 16 pathogenic genes were confirmed in 35 ARRP pedigrees, the mutations rate of RP1 gene was the highest, accounting for 14%(5/35), following were ABCA4, CRB1 and EYS gene, accounted for 11%(4/35); 18 CORD pedigrees carried 10 pathogenic genes. The mutation rate of ABCA4 gene was the highest, accounting for 28%(5/18), followed by ALMS1, PROM1, RPE65, USH2A gene, accounting for 11%(2/18). There were 5 co-exist disease-causing genes in ARRP and CORD pedigrees, which were ABCA4, CLN3, CRB1, PROM1, NRL, accounting for 42%(22/53).<p>CONCLUSION: There are similarities and crossover in the phenotype of ARRP and CORD. The pathogenic genes were overlaped. The most common overlaping gene between the two diseases is ABCA4.
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Objective@#To detect pathogenic gene variants in two Chinese families with cone-rod dystrophy(CORD).@*Methods@#After the informed consent and comprehensive ophthalmic examinations for the patients, 3 mL peripheral blood was taken from the patients’ blood vessel and DNA was extracted. The DNA was sequenced by whole-exome sequencing technology and variants were analyzed.@*Results@#Two novel compound heterozygous AIPL1 variants were detected in two patients, which were c. 923T>C(p.L308P) and c. 421C>T(p.Q141X) variants in Family 1, c. 572T>C(p.L191P) and c. 421C>T(p.Q141X) in Family 2 .@*Conclusion@#The results supported that AIPL1 gene variants are the main cause of the two CORD families. Whole-exome sequencing technology is a useful tool in the clinical differentiated diagnosis and genetic counseling for CORD patients.
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Objective To study the alteration of blood flow indexes of ophthalmic artery (OA),central retinal artery (CRA) and posterior ciliary artery (PCA) of the patients with cone-rod dystrophy (CRD).Methods The color doppler flow imaging was used in 50 CRD patients (100 eyes,CRD group) and 90 controls (180 eyes,control group) to measure the peak systolic velocity (PSV),end diastolic velocity (EDV),timeaveraged maximum velocity (TAMV),pulsatility index (PI) and resistance index (RI)in OA,CRA and PCA,respectively,and the data was obtained and analyzed statistically by one-sample t test to compare the alteration of these parameters between the CRD group and control group.Results The TAMV of OA was (14.29 ±3.88)cm · s-1 in CRD group and (12.44 ± 3.64) cm · s-1 in the control group,and the difference was statistically significant (P ＜0.05);meanwhile,the PI was 1.75 ±0.42 in CRD group and 2.02 ±0.71 in the control group,and the difference was statistically significant (P ＜0.05).Moreover,the PSV,EDV,TAMV and PI,RI of CRA was (4.60 ± 1.29) cm · s-1,(1.61 ±0.41)cm · s-1,(2.59 ±0.67)cm · s-1 and 1.11 ±0.31,0.63 ±0.10 in CRD group,respectively,and (10.82 ± 2.97) cm · s-1,(3.28 ± 1.11) cm · s-1,(5.50 ± 2.06)cm · s-1 and 1.48 ±0.49,0.71 ±0.08,in the control group,accordingly,and the differences were statistically significant (all P ＜ 0.05).Furthermore,the PSV,EDV,TAMV and PI,RI of PCA was (7.36 ± 2.18) cm · s-1,(2.28 ± 0.82) cm · s-1,(3.99 ± 1.22)cm · s-1 and 1.28 ± 0.37,0.68 ± 0.09 in CRD group,respectively,and (11.61 ± 3.41)cm · s-1,(3.34±1.25)cm · s-1,(5.83 ±1.91)cm · s-1 and 1.49 ±0.43,0.70 ±0.09 in the control group,accordingly,and the differences were statistically significant (all P ＜0.05).Conclusion Hemodynamic unusual alterations of OA,CRA and PCA in CRD patients suggest there is the correlation between the ocular blood supply and the pathological process of CRD,which remains to be observed further.