ObjectiveTo observe the transthyretin (TTR) gene mutation, protein and mRNA expression in patients with familial vitreous amyloidosis. MethodsSubjects were divided into three groups: (1) illness group: seven patients with familial vitreous amyloidosis. (2) No-illness group: 9 unaffected family members. (3) Control group: 9 healthy individuals in same area. Subjects' peripheral venous blood were collected and DNA were extracted, 4 exons of TTR gene were amplified by reverse transcription polymerase chain reaction(RT-PCR), the gene fragments were sequencing by the fluorescence labelling method. Serum TTR protein expression was detected by Western blot, and TTR mRNA in leukocyte was assayed by RT-PCR. Results4 exons of TTR gene of all samples were amplified, and DNA sequencing data showed that 7 patients and 3 subjects DNA from unaffected family members had mutated in the 3rd exon of 107th base, changing from G to C. Heterozygous mutation occurred in codon of the 83th amino acid in exon 3, namely, Gly83Arg, resulted in the change of GGC to CGC. The protein and mRNA expression of TTR was lower in illness group than no-illness group and control groups(P < 0.05). Compared with control group, TTR mRNA expression in unaffected family members groups was significant decreased(P < 0.05). ConclusionHeterozygous mutation occurred in codon of the 83th amino acid in exon 3, namely Gly83Arg, and suggested that Gly83Arg is connected with the change of TTR mRNA and protein expression.
Inherited retinal degenerations (IRD) are a group of diseases with high genetic heterogeneity and differences in inheritance patterns, age of onset and severity of visual dysfunction. It is one of the leading causes of blindness. In recent years, gene therapy becomes a popular research area in the treatment of genetic diseases due to the rapid development of gene diagnosis technology. Several clinical trials worldwide have proved the safety and effectiveness of gene therapies in IRD. Clinical application of adeno-associated virus -mediated gene therapies for Leber congenital amaurosis and choroideremia clinical trials indicate that patients' retinal functions were improved at different levels after treatment. There are a number of other IRD clinical trials ongoing currently, which bring new possibilities to treat IRD. This article reviews the pathogenesis of IRD, gene vectors and clinical trials in IRD.
Objective To investigate the polymorphism of the vitamin D receptor gene (VDR)TaqⅠin relation to diabetic retinopathy. Method Fragment length discrepant allele specific PCR(FLDAS-PCR) were used to determine VDR genetypes in 158 patients with diabetic retinopathy and in 198 normal subjects. Results The frequency distribution of VDR genotypes in diabetic retinopathy patients was 106 (67.1%) in TT, 33(20.9%) in Tt, 19(12.0%) in tt; and in normal persons was 165 (83.3%) in TT, 23(11.6%) in Tt, 10 (5.1%) in tt. There was a significant difference between diabetic retinopathy patients and normal persons in distribution of VDR gene TaqⅠgenotypes(Plt;0.05). Conclusions There is some distribution alterations of VDR gene polymorphism in diabetic retinopathy patients. (Chin J Ocul Fundus Dis, 2006, 22: 94-96)
Epigenetic mechanisms influence gene expression and function without modification of the base sequence of DNA and may generateagenetic phenotype. Epigenetic modifications include DNA methylation, histone modifications, and deployment of noncoding RNA. There is growing evidence that epigenetic mechanisms could playacrucial role in the development of diabetic retinopathy (DR). Molecular biological methods which could maintain mitochondrial homeostasis through the regulation of epigenetic mechanisms may prevent the development of DR. Epigenetic-related treatment modalities will become the new direction of targeted therapy for DR.
ObjectiveTo report the clinical findings and RS1 gene mutation analysis of a Chinese family with X-linked juvenile retinoschisis (XLRS). MethodsThe pedigree of this XLRS family was studied. Nine individuals (10 eyes of 6 males, 6 eyes of 3 females), including the proband, received ocular examination, fundus photography and optical coherence tomography (OCT). Direct DNA sequencing of the 6 exons of RS1 gene was used to detect the RS1 mutation in 12 family members. ResultsThe present pedigree included 15 members of three generations. Among them, 5 male members were diagnosed with XLRS. The retina of other 4 family members were normal, including 1 male (2 eyes) and 3 females (6 eyes). Visual acuity of these 5 patients ranged from hand movement to 0.5 and both eyes of them were involved. The age when visual acuity begins to decrease was all less than 10 years. Fundus color photographic examination showed macular radial cystoid retinoschisis and retinoschisis of the peripheral retina. OCT images showed retinoschisis in macular regions (8 eyes) or peripheral retina (6 eyes). Genetic testing showed that 1 male had no mutation in RS1 gene (p.Gly109Val). All 5 patients had a point mutation (c.326G>T) at exon 4 of RS1 gene, which cause the 109th amino acid changed from glycine to valine in the RS1 protein. A 3-year-old kid also had this mutation. The 3 females with normal retina had heterozygous mutations of Gly109Val, so they are the mutation carriers. ConclusionThe novel p.Gly109Val mutation is the causing mutation in this Chinese family with X-linked juvenile retinoschisis.