PURPOSE:To study the retinal pathologic changes and pathogenesis of relinhis pigmenlosa(RP). METHODS:The relina from a patient with autosomal dominant RP was examined by light and electron microscopy. RESULTS:Degeneration and structure disturbance almost involved in every layer of retina and were accompanied hy regional differenecs:Posterior region was more than periphery one in severity. Degeneration of retinal pigment epithelium(RPE)closely eorrelaled to that of the phmoreceplor. The uhraslrneture of the retina showed extensive and severe degeneration in the photoreeeptors ,particularly ill omer segments and mitoehondrlas. Lipofusein gramdes were accumuhtted in the cytoplagm. CONClUSIONS:These changes suggested that self-energizing system and self engulfing system of the photoreceptols were disfunctloned. （Chin J Ocul Fundus Dis,1997,13: 24-26）
Objective To investigate whether mutations exist in codon 58 and codon 347 of the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa(ADRP)． Methods Point mutations at codons 58 and 347 were detected by restriction endonuclease digestion of exons 1 and 5 amplified by polymerase chain reaction(PCR)．This method was applied to screen genomic DNAs from 57 patients of 38 families with ADRP and 60 normal controls． Results Four patients from one family of ADRP were confirmed to have a point mutation at the second nucleotide of codon 58,and 6 patients from two families of ADRP were found to have a mutation at codon 347．None of these mutations were found in 60 normal subjects． Conclusion It is suggested that molecular genetic heterogeneity exists within ADRP and some subtypes of ADRP are caused by points mutations of the rhodopsin gene． (Chin J Ocul Fundus Dis,1998,14:108-110)
ObjectiveTo identify the causative gene in a family affected with Usher syndrome (USH) with retinitis pigmentosa sine pigmento (RPSP) and to analyze the genotype-phenotype correlation.MethodsA retrospective clinical study. A 9-year-old girl with RPSP type 1F USH diagnosed in the ophthalmology clinic of Henan Provincial People's Hospital in November 2019 and her parents were included in the study. The patient had bilateral night blindness for more than 4 years, she suffered from hearing loss 7 years, and is currently binaural sensorineural deafness. The best corrected visual acuity in both eyes was 0.5+. There was showed no obvious pigmentation on the fundus. The visual acuity of the peripheral field of vision decreased. Optical coherence tomography showed that the outer layer of the peripheral retina became thinner and the ellipsoid band disappeared. On electroretinogram examination, the rod and cone system response was severely decreased. The clinical phenotype of the parents of the child were normal. The peripheral venous blood of the child and his parents were extracted, the whole genome DNA was extracted, the custom developed targeted capture kit (PS400) was used, and the next-generation sequencing technology was used to detect genetic mutations. The suspected pathogenic mutation sites were verified by Sanger; co-segregation was performed among family members. The pathogenicity of variants were evaluated according to the interpretation standards and guidelines of sequence variants. Bioinformatics techniques were used to assess the impact of variants on encoded proteins.ResultsThe results of genetic testing showed that the proband detected the PCDH15 gene c.4109dupA (p.K1370fs) (M1), c.17dupA (p.Y6_L7delinsX) (M2) compound heterozygous mutation sites, verified by Sanger sequencing, the mutations were in the family in a state of co-segregation. According to the evaluation of sequence variation interpretation standards and guidelines, M1 and M2 were pathogenic variants of the PCDH15 gene. M1 led to a complete change in the transmembrane structure of the encoded protein, and M2 caused the gene to only translate 6 amino acids, which predicted that the PCDH15 protein cannot be synthesized. According to the clinical phenotype, gene mutation pathogenicity and protein structure prediction, the final clinical diagnosis was PCDH15-related type 1F.ConclusionsPCDH15 genes c.4109dupA and c.17dupA are the pathogenic mutation sites of USH in this family. These compound heterozygous new mutations lead to the failure of normal synthesis of PCDH15 protein, which leads to ocular and ear manifestations.
ObjectiveTo use flash electroretinogram (F-ERG) and optical coherence tomography (OCT) to examine patients with primary retinitis pigmentosa (RP), and analyze the specificity of the disease on F-ERG and OCT. MethodsThirty-seven patients (74 eyes) diagnosed with primary retinitis pigmentosa in the Department of Ophthalmology, West China Hospital between September 2013 to October 2014 and 38 normal volunteers (76 eyes) were included in this study. F-ERG and OCT examinations were performed on all the patients. Then, we analyzed the differences between the two groups of subjects. ResultsFor RP patients undergoing P-ERG examination with the dark adaptation of 0.01 ERG, the latency of b wave was (73.24±6.42) ms and the amplitude of b wave was (22.87±22.48) μV; when dark adaptation of 3.0 ERG was adopted, the latency of a wave was (24.57±6.30) ms, the amplitude of a wave was (35.45±25.54) μV, the latency of b wave was (48.19±8.18) ms, and the amplitude of b wave was (119.47±50.89) μV; with the light adaptation of 3.0 ERG, the latency of a wave was (21.01±4.86) ms, the amplitude of a wave was (12.59±13.43) μV, the latency of b wave was (38.43±5.00) ms, and the amplitude of b wave was (27.19±38.12) μV. For normal volunteers undergoing F-ERG examination with the dark adaptation of 0.01 ERG, the latency of b wave was (72.63±3.49) ms and the amplitude of b wave was (86.36±21.57) μV; when the dark adaptation was 3.0 ERG, the latency of a wave was (22.88±1.62) ms, the amplitude of a wave was (210.74±43.57) μV, the latency of b wave was (42.59±2.60) ms, and the amplitude of b wave was (398.29±62.42) μV; when the light adaptation of 3.0 ERG was adopted, the latency of a wave was (16.61±0.87) ms, the amplitude of a wave was (54.26±19.64) μV, the latency of b wave was (33.29±1.11) ms, and the amplitude of b wave was (176.98±63.44) μV. There were no significant differences between the two groups when dark adaptation ERG was 0.01 (P=0.48), but for other adaptations, there were significant differences in the latency and amplitude of a and b wave between the two groups (P<0.05). The results of OCT showed that the retinal thickness of the RP patients with a range of 1 mm diameter centered on macular center concave was (218.66±74.14) mm, 3 mm diameter was (275.03±47.85) mm, and 6 mm diameter was (247.37±46.44) mm. For normal volunteers, OCT showed that the retinal thickness with a 1 mm range centered on macular center concave was (250.38±15.79) mm, 3 mm was (323.64±17.26) mm, and 6 mm was (283.44±12.50) mm. The differences between the two groups were statistically significant for each range (P<0.01). ConclusionFor patients with RP, F-ERG shows latency delay and amplitude decrease for each response, while OCT displays a thinning thickness of macular fovea. Therefore, F-ERG and OCT can not only effectively evaluate the functions of macular and the surrounding retina, but can also be used as an effective method for the diagnosis of RP.