AIM:To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies(CD) in 8 Chinese probands.· METHODS:Eight unrelated patients with stromal corneal dystrophies were recr...AIM:To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies(CD) in 8 Chinese probands.· METHODS:Eight unrelated patients with stromal corneal dystrophies were recruited in this study;all affected members were assessed by completely ophthalmologic examinations.Genomic DNA was extracted from peripheral leukocytes,17 exons of TGFBI gene and the exon of CHST6 gene were amplified by polymerase chain reaction(PCR),sequenced directly and compared with the reference database.· RESULTS:Three heterozygous mutations in TGFBI gene were identified in six patients:c.370C>T(p.Arg124Cys) was found in exon 4 of TGFBI gene in three members,c.371G>A(p.Arg124His) was found in one patient;c.1663C>T(p.Arg555Trp) was found in exon 12 in other two members.In addition,four polymorphisms with the nucleotide changes rs1442,rs1054124,rs4669,and rs35151677 were found in TGFBI gene.Mutations were not identified in the rest of 2 affected individuals in TGFBI gene or CHST6 gene.· CONCLUSION:Within these patients,R124C,R124H and R555W mutations were co-segregated with the disease phenotypes and were specific mutations for lattice corneal dystrophy type I(LCD I),Avellino corneal dystrophy(ACD,GCDⅡ),granular corneal dystrophy type I(GCD I),respectively.Our study highlights the prevalence of codon 124 and codon 555 mutations in the TGFBI gene among the Chinese stromal corneal dystrophies patients.·展开更多
To identify the underlying mutations in two unrelated British families with macular corneal dystrophy (MCD) by screening the carbohydrate sulfotransferase (CHST6) gene. Case reports and results of DNA analysis. Two su...To identify the underlying mutations in two unrelated British families with macular corneal dystrophy (MCD) by screening the carbohydrate sulfotransferase (CHST6) gene. Case reports and results of DNA analysis. Two subjects from two British families with MCD were studied. The genetic status of CHST6 was determined for all members of these MCD families. In addition, sulfated keratan sulfate (KS) assay from the probands was also undertaken. CHST6 gene was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by sequencing and restriction digestion. Enzymelinked immunosorbent assay (ELISA) was performed to assess KS presence in serum. Four compound heterozygous mutations were identified, three of which are novel. The ELISA showed that the probands were of MCD type I. These novel mutations are expected to result in loss of CHST6 function, which would account for the MCD phenotype.展开更多
Objective:To investigate gene mutations associated with three different types of corneal dystrophies(CDs),and to establish a phenotype-genotype correlation.Methods:Two patients with Avellino corneal dystrophy(ACD),fou...Objective:To investigate gene mutations associated with three different types of corneal dystrophies(CDs),and to establish a phenotype-genotype correlation.Methods:Two patients with Avellino corneal dystrophy(ACD),four patients with lattice corneal dystrophy type I(LCD I) from one family,and three patients with macular corneal dystrophy type I(MCD I) were subjected to both clinical and genetic examinations.Slit lamp examination was performed for all the subjects to assess their corneal phenotypes.Genomic DNA was extracted from peripheral blood leukocytes.The coding regions of the human transforming growth factor β-induced(TGFBI) gene and carbohydrate sulfotransferase 6(CHST6) gene were amplified by polymerase chain reaction(PCR) and subjected to direct sequencing.DNA samples from 50 healthy volunteers were used as controls.Results:Clinical examination showed three different phenotypes of CDs.Genetic examination identified that two ACD subjects were associated with homozygous R124H mutation of TGFBI,and four LCD I subjects were all associated with R124C heterozygous mutation.One MCD I subject was associated with a novel S51X homozygous mutation in CHST6,while the other two MCD I subjects harbored a previously reported W232X homozygous mutation.Conclusions:Our study highlights the prevalence of codon 124 mutations in the TGFBI gene among the Chinese ACD and LCD I patients.Moreover,we found a novel mutation among MCD I patients.展开更多
文摘AIM:To investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies(CD) in 8 Chinese probands.· METHODS:Eight unrelated patients with stromal corneal dystrophies were recruited in this study;all affected members were assessed by completely ophthalmologic examinations.Genomic DNA was extracted from peripheral leukocytes,17 exons of TGFBI gene and the exon of CHST6 gene were amplified by polymerase chain reaction(PCR),sequenced directly and compared with the reference database.· RESULTS:Three heterozygous mutations in TGFBI gene were identified in six patients:c.370C>T(p.Arg124Cys) was found in exon 4 of TGFBI gene in three members,c.371G>A(p.Arg124His) was found in one patient;c.1663C>T(p.Arg555Trp) was found in exon 12 in other two members.In addition,four polymorphisms with the nucleotide changes rs1442,rs1054124,rs4669,and rs35151677 were found in TGFBI gene.Mutations were not identified in the rest of 2 affected individuals in TGFBI gene or CHST6 gene.· CONCLUSION:Within these patients,R124C,R124H and R555W mutations were co-segregated with the disease phenotypes and were specific mutations for lattice corneal dystrophy type I(LCD I),Avellino corneal dystrophy(ACD,GCDⅡ),granular corneal dystrophy type I(GCD I),respectively.Our study highlights the prevalence of codon 124 and codon 555 mutations in the TGFBI gene among the Chinese stromal corneal dystrophies patients.·
文摘To identify the underlying mutations in two unrelated British families with macular corneal dystrophy (MCD) by screening the carbohydrate sulfotransferase (CHST6) gene. Case reports and results of DNA analysis. Two subjects from two British families with MCD were studied. The genetic status of CHST6 was determined for all members of these MCD families. In addition, sulfated keratan sulfate (KS) assay from the probands was also undertaken. CHST6 gene was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by sequencing and restriction digestion. Enzymelinked immunosorbent assay (ELISA) was performed to assess KS presence in serum. Four compound heterozygous mutations were identified, three of which are novel. The ELISA showed that the probands were of MCD type I. These novel mutations are expected to result in loss of CHST6 function, which would account for the MCD phenotype.
文摘Objective:To investigate gene mutations associated with three different types of corneal dystrophies(CDs),and to establish a phenotype-genotype correlation.Methods:Two patients with Avellino corneal dystrophy(ACD),four patients with lattice corneal dystrophy type I(LCD I) from one family,and three patients with macular corneal dystrophy type I(MCD I) were subjected to both clinical and genetic examinations.Slit lamp examination was performed for all the subjects to assess their corneal phenotypes.Genomic DNA was extracted from peripheral blood leukocytes.The coding regions of the human transforming growth factor β-induced(TGFBI) gene and carbohydrate sulfotransferase 6(CHST6) gene were amplified by polymerase chain reaction(PCR) and subjected to direct sequencing.DNA samples from 50 healthy volunteers were used as controls.Results:Clinical examination showed three different phenotypes of CDs.Genetic examination identified that two ACD subjects were associated with homozygous R124H mutation of TGFBI,and four LCD I subjects were all associated with R124C heterozygous mutation.One MCD I subject was associated with a novel S51X homozygous mutation in CHST6,while the other two MCD I subjects harbored a previously reported W232X homozygous mutation.Conclusions:Our study highlights the prevalence of codon 124 mutations in the TGFBI gene among the Chinese ACD and LCD I patients.Moreover,we found a novel mutation among MCD I patients.
