| Corneal dystrophy is the most frequent gene-inherited blinding disease of the cornea which has the incident rate of 3/100000.Corneal dystrophies involve the formation of corneal opacities that are most often characterized by bilateral .inherited , and noninflammatory ,are progressive lesions .The opacities are caused by progressive accumulation of deposits in the cornea resulting in loss of transparency and visual impairment. As the human eye ages, serious visual impairment often leading to corneal transplantation, and the disease may recrudesce after operation.Nowadays, the genetic factor is recognized as the main cause of corneal dystrophy. With the quick development of advanced molecular biological techniques, more and more corneal dystrophy associated genes and gene-mutations have been identified BIGH3 gene, which is the first nosogenetic gene of corneal dystrophy that assured by Munier and his associates in 1997, is located in 5q31.1 and includes seventeen exons. Thereinto, the four, eleven, twelve and fourteen are the mutation hot spots. Meantime, the BIGH3-related corneal dystrophy is more common in clinic, which including Granular corneal dystrophy I (CDGG I ), Avellino corneal dystrophy(CDGG II/ACD), Lattice corneal dystrophy I IIIA (LCD I , III A). In general, the BIGH3-related corneal dystrophies are bilateral and characterized by the location and structure of the opacities, However, phenotypic variability may be happened with the same gene mutation or the different gene mutation can result in the same phenotypes .At the same time, most of them are single-gene autosomal dominant inheritance and the patients' offspring have the 50% risk to have corneal dystrophy, behaving vertical transmission and a high penetrance. This research reports the characters of clinical syndrome, genetic and gene mutation of CDGG I , ACD, LCD I and LCDIIIA. Aims: 1 . With the ophthalmic, genetic genealogy investigations and analysis of theBIGH3-related corneal dystrophy cases, to understand the clinical and inherited traits. 2 With the molecular genetic study, to analyze the characteristic of thegene-mutations of the CDGG I ACD. LCD I and LCDIIIA. Methods: 1 Affected status and his (her) family were determined by common ophthalmologicexamination which including visual testing, slit-lamp examination, andnatrium-fluorescent test.2 To realize the genetic traits by pedigree analysis and protract the family tree. 3. Genomic DNA was extracted from peripheral blood of the patients which werechosen and 50 normal individuals as controls, using polymerase chain reactionand the single strand conformational polymorphism technique to analyze the genemutation. Result: 1 There were differences in the clinical syndrome between the CDGG I and ACD,LCD I and LCDIIIA. 2 There were heredity traits in the family tree which including vertical inherited,equal numbers of affected males and females. 3 R555W, A546D and 1665-1666insC mutations in exon 12 associated withCDGG I were detected while a heterozygous mutation of exon 4 with ACD wasdiscovered which was R124H. 4 R124C and T538P mutations associated with LCD I were found while twoheterozygous mutations was discovered with LCDIIIA which contained P501Tand A546T. 5 There were three polymorphisms existed in BIGH3 gene of exon8s exon11, exon12which were V327V, L472L, F540F. Conclusion:1 This study confirmed that BIGH3-related corneal dystrophy was characteristic ofheterogeneity and the tight relationship between the genetype and the phenotype;2 Single-gene autosomal dominant inheritance was demonstrated again in ourresearch.;3 Mutations of R124C, R124H, P501T, T538P, A546T, A546D and R555W of BIGH3 gene were reported in the west and east, except 1665-1666insC;4 Areas R124 and facs-4 of the KE protein represent mutational hot spots wasdemonstrated again in our patients of BIGH3-related corneal dystrophy;5 Polymorphisms of L472L F540F of BIGH3 gene were reported in the west andeast, except V327V in the east.
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