Epigenetic modifications such as DNA methylation, histone post-translational modifications, non-coding RNA are reversible, heritable alterations which are induced by environmental stimuli. Major risk factors of diabetes and diabetic complications including hyperglycemia, oxidative stress and advanced glycation end products, can lead to abnormal epigenetic modifications in retinal vascular endothelial cells and retinal pigment epithelium cells. Epigenetic mechanisms are involved in the pathogenesis of macular edema and neovascularization of diabetic retinopathy (DR), as well as diabetic metabolic memory. The heritable nature of epigenetic marks also playsakey role in familial diabetes mellitus. Further elucidation of epigenetic mechanisms in DR can open the way for the discovery of novel therapeutic targets to prevent DR progression.
Objective To analyze the new primary mutation in Chinese people with Leberprime;s hereditary optic neuropathy (LHON). Methods Genomic DNA was collected from 260 suspected LHON patients and 100 normal healthy persons. The mitochondria DNA mutation at nucleotide position (NP) 15257 and the hot spot (14452-14601 bp) of ND6 gene which include the mutations at NP (14482, 14498, 14568, 14596, 14495, and 14459) were screened by using polymerase chain reaction (PCR), heteroduplex-single strand conformation polymorphism (HA-SSCP) and restriction fragment length polymorphism (RFLP) analysis and sequencing. Primary mutation spectrum of Chinese race was analyzed. Results Eight kinds of polymorphism of mitochondria DNA were found in 260 suspected LHON patients and 100 normal healthy persons, including NP 14488C, 14518G, and 14617G which hadnrsquo;t been reported (http://www.mitomap.org/). No mutation at NP 15257, 14482, 14498, 14568, 14596, 14495, and 14459 was found. Conclusion The NP 15257A may not be the primary mutation in Chinese. Because of the race difference, 14452-14601 bp in ND6 gene may not be the hot spot in Chinese patients with LHON, and other hot spots may exist. (Chin J Ocul Fundus Dis, 2006, 22: 82-85)
RNA can be labeled by more than 170 chemical modifications after transcription, and these chemical modifications are collectively referred to as RNA modifications. It opened a new chapter of epigenetic research and became a major research hotspot in recent years. RNA modification regulates the expression of genes from the transcriptome level by regulating the fate of RNA, thus participating in many biological processes and disease occurrence and development. With the deepening of research, the diversity and complexity of RNA modification, as well as its physiological significance and potential as a therapeutic target, can not be ignored.
The rapid development of genetic diagnosis-related technologies has paved a wide road for gene therapy. Different gene therapy clinical trials for retinal disorders, including gene-replacement therapy, anti-neovascular gene therapy and opotogenetic gene therapy, have been developed and achieved fruitful results, which have gradually confirmed the efficacy and safety of adeno-associated virus (AAV)-mediated gene therapy for recessive retinal diseases. In recent years, novel gene editing technologies also shows great potential to treat dominant retinal disease, or recessive retinal disease when the therapeutic gene fragments are too long to fit into the AAV vectors. These results make it possible for most of the patients with inherited retinal diseases to be treated by the safe and effective AAV-mediated gene therapy, which will also benefit Chinese patients soon.
Objective To explore and implement a systematic, case guided online interactive training course for neurologists to improve their diagnosis and treatment of rare genetic diseases. Methods Doctors who participated in the course investigation of the neurogenetic project of the Department of Neurology of Peking Union Medical College Hospital between January and September 2021 were selected. Based on andragogy theory, a genetics training course for neurologists was developed by applying Kern’s six steps of curriculum development. According to the time of participating in the doctor’s courses, they were divided into three groups: completed all courses (10.7 h group), completed more than 1/2 courses (5.3～10.7 h group) and completed less than 1/2 courses (<5.3 h). According to the length of service, they were divided into groups of less than 10 years, 10-20 years and more than 20 years. Analyze the benefit difference of different doctors’ training time, and collect their feedback scales on the curriculum for the improvement of follow-up courses. Results A total of 54 doctors were included. Among them, 17 (31.5%) completed all courses, 29 (53.7%) completed more than 1/2 courses, and 8 (14.8%) completed less than 1/2 courses. There was a statistically significant difference among the three groups in the self-assessment improvement score (H=12.341, P=0.002). The results of pairwise comparison between groups of self-assessment improvement score showed that the <5.3 h group was lower than that of the 10.7 h group (P=0.007), and the the <5.3 h group was also lower than that of the 5.3～10.7 h group (P=0.002). 33 (61.1%) in the less than 10 years group, 16 (29.6%) in the 10-20 years group, and 5 (9.3%) in the more than 20 years group. There was no correlation between participating in work and course time (rs=0.113, P=0.418). 54 (100.0%) believed that they had more than moderate help (≥3 points). Most doctors (>90%) had a good evaluation of the curriculum. Conclusion The periodic neurogenetic re-education project is helpful for clinical diagnosis and treatment of rare neurogenetic diseases.
ObjectiveTo investigate the difference of DNA methylation before and after bariatric surgery.MethodThe relevant literatures of the research on the changes of DNA methylation level and gene expression regulation in blood and tissues before and after bariatric surgery were retrieved and reviewed.ResultsDNA methylation was an important method of epigenetic regulation in organisms and its role in bariatric surgery had been paid more and more attention in recent years. Existing studies had found that there were changes of DNA methylation in blood and tissues before and after bariatric surgery. The degree of methylation varies with different follow-up time after bariatric surgery and the same gene had different degrees of methylation in different tissues, and some even had the opposite results.ConclusionsDNA methylation levels before and after bariatric surgery are different in different tissues. And studies with larger sample size and longer follow-up time are needed, to further reveal relationship among DNA methylation, obesity, and bariatric surgery.
Objective To observe the gene mutation and clinical phenotype of patients with retinitis pigmentosa (RP) and cone rod dystrophy (CORD). Methods Thirty-seven patients with RP and 6 patients with CORD and 95 family members were enrolled in the study. The patient’s medical history and family history were collected. All the patients and family members received complete ophthalmic examinations to determine the phenotype, including best corrected visual acuity, slit lamp microscope, indirect ophthalmoscopy, color fundus photography, optical coherence tomography, full-field electroretinogram, and fluorescein fundus angiography. DNA was abstracted from patients and family members. Using target region capture sequencing combined with next-generation sequencing to screen the 232 candidate pathogenic mutations. Polymerase chain reaction and direct sequencing were used to confirm the pathogenic pathogenic mutations and Co-segregation is performed among members in the family to determine pathogenic mutation sites. The relationship between genotype and clinical phenotype of RP and CORD was analyzed. Results Of the 37 patients with RP, 13 were from 6 families, including 4 families with autosomal dominant inheritance, 2 families with autosomal recessive inheritance, and 3 in 6 families were detected pathogenic gene mutations. 24 cases were scattered RP. Six patients with CORD were from four families, all of which were autosomal recessive. Of the 43 patients, 21 patients were detected the pathogenic gene mutation, and the positive rate was 48.8%. Among them, 15 patients with RP were detected 10 pathogenic gene mutations including USH2A, RP1, MYO7A, C8orf37, RPGR, SNRNP200, CRX, PRPF31, C2orf71, IMPDH1, and the clinical phenotype included 10 typical RP, 2 cases of RPSP, 3 cases of Usher syndrome type 2 and 6 cases of CORD patients were all detected pathogenic gene mutations, including 2 cases of ABCA4, 2 mutations of RIMS1 gene, 1 case of CLN3 gene mutation, and 1 case of CRB1 and RPGR double gene mutation. Conclusions RP and CORD are clinically diverse in genotype and clinically phenotypically similar. For patients with early RP and CORD, clinical phenotype combined with genetic analysis is required to determine the diagnosis of RP and CORD.
Objective To observe the genetic predisposition of complement C5 gene polymorphisms in proliferative diabetic retinopathy (PDR) in Chongqing Han population. Methods 400 type 2 diabetes (T2D) patients (case group) and 600 age- and sex-matched healthy controls (control group) were enrolled in this study. There were 8 PDR patients in case group. All the subjects were Han ethnic people. The immune-related representative SNP locus of C5 gene including rs2269067, rs7040033, rs7027797 were screened by linkage disequilibrium analysis. Locus rs1017119 was selected by TagSNP and was around the above three loci. Subjects′ peripheral venous blood was collected and DNA was extracted. Genotyping was examined by PCR-restriction fragment length polymorphism method. The level of C5 plasma protein was measured by enzyme-linked immunoabsorbent assay. Results The frequency of GG genotype of rs2269067 was significantly increased in PDR patients in cases group compared with controls (Pc=3.4×10-5, OR=1.87, 95%CI=1.43 - 2.44；P=3.1×10-6). There was no differences in frequency of G, CC and CG genotype of rs2269067 between two groups (P=1.4×10-4, 1.000, 1.0×10-6). There were no differences in frequency of G, CC, CG, GG genotype of rs7040033, rs1017119, and rs7027797 between two groups (P > 0.05). The production of C5 plasma protein was significantly increased in case group as compare with control group (P=0.0004). An increased production of C5 plasma protein was observed in rs2269067 GG genotype cases compared to CG or CC cases (P=0.003, 0.001). Conclusion C5 rs2269067 GG genotype may be associated with the PDR of T2D in Chongqing Han population.
X-linked retinoschisis (XLRS) is a rare X-linked inherited retinal disorder, caused by mutations in retinoschisin 1 (RS1) gene. Three XLRS mice were established, providing ideal systems to study the mechanism and treatment methods for XLRS. RS1 gene mutations can induce abnormal secretion or adhesion function of RS1 protein. In the past year, phase I clinical trials for XLRS has begun in USA, using adeno associated virus (AAV, AAV8 or AAV2)-mediated gene delivery. With the rapid development of new generation of AAV vector that can transduce more retinal cells through intravitreous delivery, gene therapy for XLRS will have a brighter future.
Primary cardiac tumors, which originate from the heart, are uncommon and can be classified as benign or malignant, with the majority being benign. Malignant primary cardiac tumors have a poor prognosis. Benign ones may also cause severe hemodynamic and electrophysiological consequences, but the prognosis is generally good if they are detected early and treated properly. In recent years, researches on the genetic and molecular causes of primary cardiac tumors have yielded some promising breakthroughs, with some of them already being translated into clinical practice. This article reviews research progress and its use in precise diagnosis and targeted therapy from the perspective of DNA, RNA, and protein changes, as well as prospects the promising research directions in the future.