ObjectiveTo observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP). MethodsA retrospective clinical study. Two patients (proband) and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study. Two families have no blood relationship and were both Han Chinese. Detailed ocular and systemic medical history and specialized examinations were performed for all members, including color fundus photography, fundus autofluorescence (FAF), and full field electroretinogram (ff-ERG) examination. The peripheral venous blood of all members was collected, and genomic DNA was extracted. Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology. Sanger sequencing was used to verify the pathogenic genes in the two pedigrees. The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants. ResultsThe two probands were male, aged 9 and 7 years, respectively. The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia. The proband (Ⅱ2) in family 1 had a pale red color on the optic disc, with leopard-like changes in the posterior pole and thinner retinal arteries. FAF showed mottled fluorescence attenuation outside the macular vascular arch. There was no significant waveform in both bright and dark visual responses of ff-ERG. He also had 6-toed deformity of both feet, renal cysts, and a slightly overweight body. The clinical diagnosis was non-pigmentary retinitis pigmentosa. The proband of family 2 (Ⅱ1) had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus. FAF showed uneven enhancement in the fovea. ff-ERG showed severe abnormalities in dark and light response, with significant decrease and delay in b-wave amplitude and latency. He had no other systemic abnormalities. The clinical diagnosis was binocular RPSP. There were no abnormal ocular and systemic manifestations in the two family members. Gene sequencing revealed a homozygous mutation (c.534+1G>T) of BBS2 gene, which was inherited from the mother and father respectively. Based on clinical manifestations and genetic testing results, the final diagnosis was Bardet Biedl syndrome. The genetic sequencing results confirmed a novel compound heterozygous mutation (c.950T>G: p. Leu317Arg missense mutation and c.849+1G>C splicing mutation) of BBS7 gene. His father (Ⅰ1) and mother (Ⅰ2) carried M1 heterozygous variants. Combined with the clinical manifestations and genetic testing results, the final diagnosis was Bardet-Biedl syndrome (BBS). Family 2 proband (Ⅱ1) carried the BBS7 gene C.950T>G (p.Leu317Arg) (M2) missense variation and C.849 +1G>C (M3) splice site variation. His father (Ⅰ1) and mother (Ⅰ2) carried M3 shear site variation and M2 missense variation, respectively. The two families all fit the autosomal recessive inheritance pattern, and the genotype and clinical phenotype were coseparated. According to ACMG guidelines, M1, M2 and M3 were all identified as possible pathogenic variants. ConclusionsBBS2 gene M1 homozygous variation and BBS7 gene M2, M3 complex heterozygous variation are the possible pathogenic genes in family 1 and family 2, respectively. Two families are affected by BBS and RPSP, respectively.
Objective To observe the mutifocal electroretinogram (mfERG) characteristics of rod and cone cells in patients with retinitis pigmentosa (RP) and to evaluate the function of photosensory cell.Methods The mfERG recording technique for rod cell in eight normal subjects (eight eyes) were established and the influence of different brightness lightstimulus in P1 wave amplitude were analyzed. The cone and rod cells mfERG of 38 eyes in 19 patients were recorded and then calculated positive ratio from local signalnoise ratio. The average visual acuity and P1 wave amplitude density of cone mfERG in different types were compared and statistically analyzed. Meanwhile, the changes in P1 wave amplitude of cone and rod mfERG in four quadrants also compared and analyzed. Results Rod cell mfERG in normal subjects can be recorded stably by using blue flashes with low light intensity as 0.04 cd/m2. In patients with RP, the cone and rod cells mfERG can be detectd 65.79% and 10.51% respectively. P1 wave amplitude density in type I of cone cell mfERG was significantly higher than that in type II (t=5.21,P=0.000). There were no differences in average visual acuity (t=1.15, P=0.612). P1 wave amplitude density in type I was negatively related to logMAR visual acuity （r=-0.48，P=0.04）.The comparison of rod and cone cells mfERG in local wave characteristics showed that P1 wave amplitude densities had spatial relationship in each area. Conclusions The results suggested highly variable central responses in cone cell in RP patients, higher positive recorded ratio in cone cell than rod cell and spatial correspondence between the function of reserved cone and rod cells.
Objective To investigate the cilinical value of indocyanine green angiography(ICGA) in patients with Vogt-Koyanagi-Harada syndrome(VKH). Methods Fundus fluorescein angiography(FFA) and indocyanine green angiography(ICGA) were used for comparative analyses in 26 cases(52 eyes)of VKH. Results In the acute stage of VKH,FFA revealed the multifocal leakage in the pigment epithelium and the multifocal serous retinal detachment,and the typical FFA manifestations disappeard following treatment．In the acute stage of the disease the ICGA showed:(1)numerous patchy areas of hypofluorescence and decreased flurescence in large and middle choroidal vessels(66.7%);(2)dilatation of the choroidal vessels(70.8%)and(3)in latephase of ICGA,the patchy areas of hyperfluorescence(79.2%).During the recovery stage of the disease,the abnormal undings in ICGA were resolved slower than those found in FFA. Conclusions ICGA may assist in providing valuable informations on choroidal circulation of VKH and be useful in evaluating the curative effects． (Chin J Ocul Fundus Dis,20000,16:9-11)
Objective:To observe the intervention effect of the tetra methylpyraz ine on the rds mice with retinitis pigmentosa. Methods:A total of 84 rds mice were randomly divided into 2 groups, with 42 mice in each group. The mice in the experimental group underwent intraperitoneal cavity injection with hydrochlor i c tetramethylpyrazine (80 mg/kg, twice per day) at the date of birth and till 35 days after birth, whereas the normal saline was injected into the intraperito n eal cavity of rats in the control group. The mice were sacrificed 0, 3, 7, 14, 2 1, 28, 35 days after birth, and the eyeballs were enucleated for the routine pat hologic examination with the light microscope. The apoptosis of photoreceptor ce ll nuclei was detected by terminal deoxynucleotidyl transferasemediated dUTP n i ck endlabeling (TUNEL) technigue and the expression of bcl2 in retina was de tect by immunohistochemistry method. Results:The results of li ght microscopy s howed that the layer number of retinal photoreceptor cell nuclei with tetramethy lpyrazine treatment was increased 14, 21, 28, 35 days after the treatment compar ed with that in the control group（P＜0.01）. The results of electron-micro scope suggested that tetramethylpyrazine might reduce lesions in the photoreceptor cells and the destruction of the disc member, mitochondrion，and outer limiting me mbrane in the photoreceptor outer segment in rds mice. The apoptosis of the phot oreceptor cell nuclei reduced in rds mice 3, 7, 14, 21, 28 and 35 days after the treatment compared with that in the control group （P＜0.01）. The express ion of bcl-2 in the matrix of retinal photoreceptor cell nuclei and its inner and o u ter segments increased significantly in rds mice 3，7, 14, 21, 28 and 35 days af ter the treatment （P＜0.05）. Conclusions:Tetramethylpyra zine might reduce ret inal photoreceptor apoptosis by upregulating the expression of bcl-2 in the m at rix of retinal photoreceptor cell nuclei or its inner and outer segments in rds mice.
Objective To analyze the pathogenic gene and clinical phenotypes of a family affected with rare sector retinitis pigmentosa (sector RP). Methods A retrospective clinical study. A patient with sector RP diagnosed in Renmin Hospital of Wuhan University and his parents were included in the study. Detailed medical history was collected; best corrected visual acuity (BCVA), fundus color photography, autofluorescence (AF), visual field, optical coherence tomography (OCT), electroretinogram, fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) examination were performed. The peripheral venous blood of the patient and his parents were collected, and DNA was extracted. A whole exon sequencing was used for the proband. The mutations were verified by targeted Sanger sequencing and quantitative polymerase chain reaction. Bioinformatics analysis and cosegregation analysis were performed. ResultsThe proband, a 17-year-old male, had presented with gradually decreased vision in the past 2 years with BCVA of 0.4 in both eyes. Retinal vessels attenuation and macular dystrophy without obvious pigmentation on the fundus were observed. AF showed, in bilateral eyes, a symmetrical hypo-autofluorescent region only in the inferonasal quadrant and “petal-like” hyper-AF macula. The visual field examination showed defects in the superotemporal quadrant corresponding to the affected retina. OCT showed loss of the photoreceptor layer except for the foveal region. Electroretinogram examination presented reduced scotopic wave peaks and extinct photopic response. FFA and ICGA showed the atrophy retinal pigment epithelium around the optic disk and in the inferior retina. The clinical phenotypes of the parents were normal. The whole exon sequencing identified one mutation in SPATA7 gene, c.1112T>C (p.Ile371Thr) in exon10 and a copy number variation in trans. The missense mutation resulted in the change of isoleucine to threonine at amino acid 371 in the encoded SPATA7 protein, and the mother carried this heterozygous mutation c.1112T>C. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for classification of genetic variants, the missense mutation was classified as the uncertain significance. The CNV, originating from his father, contributed to the loss of exon10 and was confirmed as the likely pathogenic variant. ConclusionsThe macula can be involved in sector RP, leading to the macular dystrophy. The missense variant in SPATA7 gene, c.1112T>C (p.Ile371Thr), might be a pathogenic mutation site in this pedigree.
Cilia are hair-like protuberance on cells of the human body that play a vital role in organs generation and maintenance. Abnormalities of ciliary structure and function affect almost every system of the body, such as the brain, eyes, liver, kidney, bone, reproductive system and so on. Retinal photoreceptor cells are one of sensory neurons which convert light stimuli into neurological responses. This process, called phototransduction, takes place in the outer segments (OS) of rod and cone photoreceptors. OS are specialized sensory cilia, and disruptions in cilia genes, which are causative in a growing number of non-syndromic retinal dystrophies, such as retinitis pigmentosa, Leber’s congenital amaurosis. These syndromes are genetically heterogeneous, involving mutations in a large number of genes. They show considerable clinical and genetic overlap. At present, there are few researches on retinal ciliopathies and clinical treatment strategy. This review shows a comprehensive overview of ciliary dysfunction and visual development related diseases, which contributes to understand the characteristics of these diseases and take early intervention in clinic.