Corneal dystrophy is a common type of hereditary corneal diseases. It includes many types, which have varied pathology, histology and clinical manifestations. Recently, the examination techniques of ophthalmology and ...Corneal dystrophy is a common type of hereditary corneal diseases. It includes many types, which have varied pathology, histology and clinical manifestations. Recently, the examination techniques of ophthalmology and gene sequencing advance greatly, which do benefit to our understanding of these diseases. However, many aspects remain still unknown. And due to the poor knowledge of these diseases, the results of the treatments are not satisfactory. The purpose of this review was to summarize the clinical, histological and genetic characteristics of different types of corneal dystrophies.展开更多
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
CRISPR/Cas,an adaptive immune system in bacteria,has been adopted as an efficient and precise tool for site-specific gene editing with potential therapeutic opportunities.It has been explored for a variety of applicat...CRISPR/Cas,an adaptive immune system in bacteria,has been adopted as an efficient and precise tool for site-specific gene editing with potential therapeutic opportunities.It has been explored for a variety of applications,including gene modulation,epigenome editing,diagnosis,mRNA editing,etc.It has found applications in retinal dystrophic conditions including progressive cone and cone-rod dystrophies,congenital stationary night blindness,X-linked juvenile retinoschisis,retinitis pigmentosa,age-related macular degeneration,leber’s congenital amaurosis,etc.Most of the therapies for retinal dystrophic conditions work by regressing symptoms instead of reversing the genemutations.CRISPR/Cas9 through indel could impart beneficial effects in the reversal of gene mutations in dystrophic conditions.Recent research has also consolidated on the approaches of using CRISPR systems for retinal dystrophies but their delivery to the posterior part of the eye is a major concern due to high molecular weight,negative charge,and in vivo stability of CRISPR components.Recently,non-viral vectors have gained interest due to their potential in tissue-specific nucleic acid(miRNA/siRNA/CRISPR)delivery.This review highlights the opportunities of retinal dystrophies management using CRISPR/Cas nanomedicine.展开更多
Objective: To review the long-term outcomes for 155 women with a vulvar dystrophy (VD) who attended the Royal Brisbane Hospital Vulvar Clinic between 1976 and 1988. Methods: VD data from Vulvar Diseases Clinic were re...Objective: To review the long-term outcomes for 155 women with a vulvar dystrophy (VD) who attended the Royal Brisbane Hospital Vulvar Clinic between 1976 and 1988. Methods: VD data from Vulvar Diseases Clinic were reviewed and analysed using the computer software Statistical package for the Social Sciences (SPSS) 11.0. Results: Of 155 patients 94 had Lichen Sclerosus (LS), 41 Lichen Simplex Chronicus (LSC) and 20 Mixed Dystrophy (MD). Three patients developed squamous cell carcinomas of the vulva between 10 and 26 years after presentation with a VD. To date only one of these three patients remains alive following treatment. Conclusion: The need for long term follow up is stressed and any of the three types of VD may become malignant. Time from diagnosis to malignant change is not predictive. VD treatments seem to go through phases with the application of potent steroid creams having stood the test of time.展开更多
The advent of next generation sequencing(NGS) tech-niques has greatly simplified the molecular diagnosis and gene identification in very rare and highly heterogeneous Mendelian disorders. Over the last two years, thes...The advent of next generation sequencing(NGS) tech-niques has greatly simplified the molecular diagnosis and gene identification in very rare and highly heterogeneous Mendelian disorders. Over the last two years, these approaches, especially whole exome sequencing(WES), alone or combined with homozygosity mapping and linkage analysis, have proved to be successful in the identification of more than 25 new causative retinal dystrophy genes. NGS-approaches have also identified a wealth of new mutations in previously reported genes and have provided more comprehensive information concerning the landscape of genotype-phenotype correlations and the genetic complexity/diversity of human control populations. Although whole genome sequencing is far more informative than WES, the functional meaning of the genetic variants identified by the latter can be more easily interpreted, and final diagnosis of inherited retinal dystrophies is extremely successful, reaching 80%, particularly for recessive cases. Even considering the present limitations of WES, the reductions in costs and time, the continual technical improvements, the implementation of refined bioinformatic tools and the unbiased comprehensive genetic information it provides, make WES a very promising diagnostic tool for routine clinical and genetic diagnosis in the future.展开更多
Muscular dystrophies(MD) comprise a heterogeneous group of hereditary myopathic diseases.In this group,myotonic MD is associated with an increased cancer risk.However,the cancer risk in other types of MD is unclear.To...Muscular dystrophies(MD) comprise a heterogeneous group of hereditary myopathic diseases.In this group,myotonic MD is associated with an increased cancer risk.However,the cancer risk in other types of MD is unclear.To address this gap in knowledge,we assessed data obtained from the Taiwan Health Insurance Program database.A total of 1,272 patients with MD diagnosed between 1997 and 2009 were enrolled.They were followed up for cancer during the same period by record linkage with the cancer certification in Taiwan.Age-and sex-standardized incidence ratios(SIRs) of overall and site-specific cancers were calculated.For congenital and progressive hereditary MD,there were 685 and 505 cases(males:69.5% and 80.6%),the median ages at diagnosis were 16 and 13 years,and the mean follow-up durations were 7.12 and 5.06 years,respectively.In addition,cancers were developed in 10 patients with congenital MD and 3 patients with progressive hereditary MD.Female MD patients exhibited an increased cancer risk,yielding an SIR of 3.37 [95% confidence interval(CI) = 1.38-8.25] in congenital MD and 2.95(95% CI = 0.95-9.19) in hereditary progressive MD.Site-specific cancer SIRs were not powered to be significantly different.In conclusion,genetic defects in hereditary MD may increase cancer risks in females and a sex difference should be further investigated.展开更多
文摘Corneal dystrophy is a common type of hereditary corneal diseases. It includes many types, which have varied pathology, histology and clinical manifestations. Recently, the examination techniques of ophthalmology and gene sequencing advance greatly, which do benefit to our understanding of these diseases. However, many aspects remain still unknown. And due to the poor knowledge of these diseases, the results of the treatments are not satisfactory. The purpose of this review was to summarize the clinical, histological and genetic characteristics of different types of corneal dystrophies.
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.·
基金the Indian Council of Medical Research (ICMR) for financial support through senior research fellowship (SRF) to DKS (file no. 45/66/2019Nan/BMS)and junior research fellow to MS (file no. 3/1/3/JRF2019/HRD(LS))support from the Department of Biotechnology, Ministry of Science and Technology (DBT), Government of India to DC through project grant (BT/PR26897/NNT/28/1489/2017)
文摘CRISPR/Cas,an adaptive immune system in bacteria,has been adopted as an efficient and precise tool for site-specific gene editing with potential therapeutic opportunities.It has been explored for a variety of applications,including gene modulation,epigenome editing,diagnosis,mRNA editing,etc.It has found applications in retinal dystrophic conditions including progressive cone and cone-rod dystrophies,congenital stationary night blindness,X-linked juvenile retinoschisis,retinitis pigmentosa,age-related macular degeneration,leber’s congenital amaurosis,etc.Most of the therapies for retinal dystrophic conditions work by regressing symptoms instead of reversing the genemutations.CRISPR/Cas9 through indel could impart beneficial effects in the reversal of gene mutations in dystrophic conditions.Recent research has also consolidated on the approaches of using CRISPR systems for retinal dystrophies but their delivery to the posterior part of the eye is a major concern due to high molecular weight,negative charge,and in vivo stability of CRISPR components.Recently,non-viral vectors have gained interest due to their potential in tissue-specific nucleic acid(miRNA/siRNA/CRISPR)delivery.This review highlights the opportunities of retinal dystrophies management using CRISPR/Cas nanomedicine.
文摘Objective: To review the long-term outcomes for 155 women with a vulvar dystrophy (VD) who attended the Royal Brisbane Hospital Vulvar Clinic between 1976 and 1988. Methods: VD data from Vulvar Diseases Clinic were reviewed and analysed using the computer software Statistical package for the Social Sciences (SPSS) 11.0. Results: Of 155 patients 94 had Lichen Sclerosus (LS), 41 Lichen Simplex Chronicus (LSC) and 20 Mixed Dystrophy (MD). Three patients developed squamous cell carcinomas of the vulva between 10 and 26 years after presentation with a VD. To date only one of these three patients remains alive following treatment. Conclusion: The need for long term follow up is stressed and any of the three types of VD may become malignant. Time from diagnosis to malignant change is not predictive. VD treatments seem to go through phases with the application of potent steroid creams having stood the test of time.
基金Supported by Grants SAF2013-49069-C2-1-R(Marfany G and Gonzàlez-Duarte R)BFU2010-15656(Marfany G)(Ministerio de Ciencia e Innovación)+3 种基金SGR2014-0932(Generalitat de Catalunya)CIBERER(U718)Retina Asturias(Gonzàlez-Duarte R)ONCE(Gonzàlez-Duarte R)
文摘The advent of next generation sequencing(NGS) tech-niques has greatly simplified the molecular diagnosis and gene identification in very rare and highly heterogeneous Mendelian disorders. Over the last two years, these approaches, especially whole exome sequencing(WES), alone or combined with homozygosity mapping and linkage analysis, have proved to be successful in the identification of more than 25 new causative retinal dystrophy genes. NGS-approaches have also identified a wealth of new mutations in previously reported genes and have provided more comprehensive information concerning the landscape of genotype-phenotype correlations and the genetic complexity/diversity of human control populations. Although whole genome sequencing is far more informative than WES, the functional meaning of the genetic variants identified by the latter can be more easily interpreted, and final diagnosis of inherited retinal dystrophies is extremely successful, reaching 80%, particularly for recessive cases. Even considering the present limitations of WES, the reductions in costs and time, the continual technical improvements, the implementation of refined bioinformatic tools and the unbiased comprehensive genetic information it provides, make WES a very promising diagnostic tool for routine clinical and genetic diagnosis in the future.
文摘Muscular dystrophies(MD) comprise a heterogeneous group of hereditary myopathic diseases.In this group,myotonic MD is associated with an increased cancer risk.However,the cancer risk in other types of MD is unclear.To address this gap in knowledge,we assessed data obtained from the Taiwan Health Insurance Program database.A total of 1,272 patients with MD diagnosed between 1997 and 2009 were enrolled.They were followed up for cancer during the same period by record linkage with the cancer certification in Taiwan.Age-and sex-standardized incidence ratios(SIRs) of overall and site-specific cancers were calculated.For congenital and progressive hereditary MD,there were 685 and 505 cases(males:69.5% and 80.6%),the median ages at diagnosis were 16 and 13 years,and the mean follow-up durations were 7.12 and 5.06 years,respectively.In addition,cancers were developed in 10 patients with congenital MD and 3 patients with progressive hereditary MD.Female MD patients exhibited an increased cancer risk,yielding an SIR of 3.37 [95% confidence interval(CI) = 1.38-8.25] in congenital MD and 2.95(95% CI = 0.95-9.19) in hereditary progressive MD.Site-specific cancer SIRs were not powered to be significantly different.In conclusion,genetic defects in hereditary MD may increase cancer risks in females and a sex difference should be further investigated.
