Objective To observe the mutation frequency and the characteristics of rentinitis pigmentosa (RP)1 gene in the Chinese patients with autosomal dominant (AD) RP or sporadic RP (SRP), and to evaluate their potential effects on the pathogenesis of RP. Methods Fifty-five members from 7 Chinese families with ADRP, 30 patients with SRP, and 75 healthy adults were recruited. Polymerase chain reaction (PCR) and direct DNA sequencing were used to detect the sequence mutation in the entire coding region and splice sites of RP1 gene. Univariate analysis and multivariate analysis were used to detect the effect of RP1 gene mutation sites on RP. Results Four coding sequence variants were detected in the codes of 852，872，921 and 939 at the exon 4 of RP1 gene. The R872H alteration, which was found in both ADRP families and patients with SRP, showed positive correlation with RP confirmed by the multivariate logistic regression analysis. The P903L alteration was only found in ADRP families but not in the patients with SRP or the healthy adults. Conclusions The R872H alteration in the RP1 gene is likely to increase the risk of RP, and may be a susceptible gene of RP. Whether the P903L alteration is a diseasecausing factor needs to be further studied.
Objective To investigate the disease-causing gene of Stargardt disease. Method Fifteen patients with Stargardt disease were analyzed with 11 primers of the 11 exons of ABCR gene by using PCR-SSCP and DNA direct sequencing techniques. Results Three newly detected disease-causing mutations were found. Among those mutations, one is a frameshift mutation and others are single base transition. Conclusion This research confirmed that ABCR gene is associated with Stargardt disease, and 3 new mutations of ABCR gene were found. (Chin J Ocul Fundus Dis,2000,16:240-243)
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.
ObjectiveTo analyze effects of histone demethylase Jumonji-domaincontaining protein 3 (JMJD3) in macrophages in order to provide a new target for treatment of macrophage-related inflammatory reactions, autoimmune diseases, and organ transplantation rejection.MethodThe related literatures of researches on the effects of JMJD3 in the macrophages in recent years were searched and reviewed.ResultsThe macrophages played the important roles in maintaining tissue homeostasis and host response, clearing pathogens and apoptotic cells, and promoting tissue repair and wound healing. The JMJD3 could regulate the balance of M1 and M2 types of macrophages through the different ways and had different effects on the polarization of M2 macrophages when it was stimulated by the different extracellular substances. In some immune diseases and wound repairing, the JMJD3 could not only promote the inflammatory responses, but also polarize the M2 macrophages so as to inhibit the inflammation and promote the tissue repair. Clinically, the JMJD3 expression might be different in the different diseases and its low or high expression both might be involved in the occurrence of diseases.ConclusionHistone demethylase enzyme JMJD3 is involved in macrophage polarization and expression of inflammatory genes, but there are still many problems that require further to be investigated.
Objective To analyze the correlation between HLA-A and B genotypes and maculopapular exanthema (MPE) caused by Carbamazepine (CBZ) and Oxcarbazepine (OXC), and to explore the genetic risk factors of MPE. Methods Patients with MPE (rash group) and patients without MPE (non-rash group) after taking CBZ or OXC were retrospectively collected from January 2016 to October 2021 in the Second Affiliated Hospital of Guangzhou Medical University. DNA was extracted from peripheral blood. HLA-A and HLA-B alleles were sequenced by high resolution sequencing, and a case-control study was conducted to analysis the correlations between MPE and HLA genotypes. Results A total of 100 patients with CBZ-MPE, 100 patients with CBZ-tolerant, 50 patients with OXC-MPE, and 50 patients with OXC-tolerant were collected. There was no significant difference in age and sex between CBZ, OXC rash groups and non-rash groups The average latency of CBZ-rash group was (11.31±11.00) days and their average dosage was (348.46±174.10) mg; the average latency of OXC-rash group was (11.67±10.34) days and their average dosage was (433.52±209.22) mg [equivalent to CBZ (289.01±139.48 mg)], showing no significant difference in latency and dosage between CBZ and OXC (P>0.05). The positive rates of HLA-A*24:02 and A*30:01 in CBZ-rash group were 28% and 6%, respectively, which were significantly higher than those in CBZ-non rash group (16% and 0%, both P=0.04). The positive rate of HLA-B*40:01 in CBZ-rash group was 18%, which was significantly lower than that in CBZ-non rash group (40%, P<0.001). No association between HLA-A or B genotype and OXC-rash was found yet. When pooled, it was still found that the positive rates of HLA-A*24:02 and A*30:01 in the rash group were higher than those in the non-rash group, while the positive rate of HLA-B*40:01 in the rash group was lower than that in the non-rash group, and the difference was statistically significant (P<0.05). Conclusions HLA-A*24:02 and A*30:01 were associated with MPE caused by CBZ, and may be common risk factors for aromatic antiepileptic drugs.
Congenital chest deformity is caused by abnormal development of spine or ribs, resulting in sternal depression or protrusion. Pectus carinatum and pectus excavatum are the most common diseases in clinic, which can either be accompanied by other syndromes or exist alone. The genetic factors of congenital thoracic deformity can be related to single gene mutation, polygene mutation and chromosome aberration. Common clinical congenital thoracic deformity with syndromes, such as Marfan syndrome and Noonan syndrome, often have relatively fixed and clear pathogenic genes. The genetic pathogenesis of non-syndromic and independent congenital thoracic malformations is usually diverse, and treatments for syndromic and non-syndromic congenital thoracic deformity are different. Therefore, it is necessary for us to differentiate syndromic and non-syndromic congenital thoracic deformities in basic research, clinical diagnosis and treatment.
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)