Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TGFBI gene mutation analysis in a Chinese pedigree of Avellino corneal dystrophy.

ABSTRACT: AIM:To analyze phenotype and genotype of a Chinese pedigree with Avellino corneal dystrophy (ACD). METHODS:Complete ophthalmic examinations were performed on all the family members. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database. RESULTS:A single heterozygous G>A (R124H) point mutation was identified in exon 4 of TGFBI in three affected members and two unaffected children who were offsprings of the affected members, but not in the other family members. CONCLUSION:Mutation R124H in TGFBI was identified in this pedigree and appeared to be the disease causing mutation. Atypical phenotype and low penetrance was observed in this pedigree.

SUBMITTER: Xie AR

PROVIDER: S-EPMC3340809 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

TGFBI gene mutation analysis in a Chinese pedigree of Avellino corneal dystrophy.

Xie Ai-Rui AR Cai Su-Ping SP Yang Yin Y Fan Yin-Chuan YC Yu Wen-Han WH Guo Li-Heng LH Yang Qiao-Na QN Zhu Jin J Liu Xu-Yang XY

International journal of ophthalmology 20110618 3

<h4>Aim</h4>To analyze phenotype and genotype of a Chinese pedigree with Avellino corneal dystrophy (ACD).<h4>Methods</h4>Complete ophthalmic examinations were performed on all the family members. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database.<h4>Results</h4>A single heterozygous G>A (R124H) point mutation was identified in exon 4 of TGFBI in three affected members and two unaffected children who were offsprings of the affected memb ...[more]

PMID: 22553661

Similar Datasets

An Arg124His mutation in TGFBI associated to Avellino corneal dystrophy in a Chinese pedigree.

Project description:To identify the gene mutation underlying Avellino corneal dystrophy in a four-generation Chinese pedigree.Patients from the affected family underwent detailed clinical examination involving slit-lamp photography and confocal microscopy. Genomic DNA extracted from peripheral leukocytes was amplified using touch-down PCR for gene scanning. Two-point linkage analysis and haplotyping were performed to map the relevant chromosome region. The candidate gene in this region was sequenced to screen out the disease-causing mutation.Patients in the pedigree were diagnosed with Avellino corneal dystrophy. Using linkage analysis, the responsible gene was mapped to chromosome 5q31.2 with a maximum LOD (log odds) score (Z(max)) of 3.23 at D5S479 (?(max)=0.0). Haplotypes constructed from 11 microstallite markers identified the disease-linked chromosome region as being below D5S808. Sequencing of TGFBI (transforming growth factor-beta induced gene), a known gene in this region, revealed a heterozygous transition (c.418 G>A) in exon 4 resulting in Arg124His (R124H) being co-segregated with the disease in affected family members but not in the unaffected members or the 50 unrelated controls.Our study demonstrated that a G>A transition in Arg124His of TGFBI was responsible for Avellino corneal dystrophy in a Chinese pedigree. This result further supports the importance of TGFBIp in maintaining transparency of the cornea.

| S-EPMC3244477 | biostudies-literature

TGFBI gene mutation analysis in a Chinese pedigree of Reis-Bucklers corneal dystrophy.

Project description:PurposeTo analyze transforming growth factor beta-induced (TGFBI) gene mutations in a Chinese pedigree with Reis-Bücklers dystrophy (RBCD).MethodsIn a four-generation Chinese family with Reis-Bücklers dystrophy, six members were patients and the rest were unaffected. All members of the family underwent complete ophthalmologic examinations. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database. The sequencing results were reconfirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsA single heterozygous C>T (R124C) point mutation was found in exon 4 of TGFBI in all six members of the pedigree affected with RBCD, but not in the unaffected members.ConclusionsWithin this pedigree, RBCD segregates with the R124C variance, which is a known mutation for lattice corneal dystrophy type I. Therefore, along with G623D and R124L, the R124C mutation in TGFBI is also found to be responsible for RBCD.

| S-EPMC2847680 | biostudies-literature

Arg124Cys mutation of the TGFBI gene in a Chinese pedigree of Reis-Bucklers corneal dystrophy.

Project description:AimTo analyze mutations in transforming growth factor beta-induced (TGFBI) gene in a Chinese pedigree with Reis-Bücklers corneal dystrophy (RBCD, also known as GCD3).MethodsIn a five-generation Chinese family, eight members were identified with RBCD and the rest were unaffected. All members of the family underwent complete ophthalmologic examinations. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database.ResultsA single heterozygous C>T (R124C) point mutation was found in exon 4 of TGFBI in all the affected members of the pedigree, but not in the unaffected members.ConclusionR124C which was a known mutation for lattice corneal dystrophy type I, segregated with the RBCD in this pedigree. This elucidated the correlation between genotype and phenotype in a Chinese family of RBCD.

| S-EPMC3340806 | biostudies-literature

Reduced penetrance in familial Avellino corneal dystrophy associated with TGFBI mutations.

Project description:PurposeTo characterize the clinical phenotype, histopathological features, and molecular genetic basis of an Avellino corneal dystrophy (ACD) in a Chinese family.MethodsA complete ophthalmologic examination was performed in 21 individuals (6 affected and 15 unaffected) of the four-generation family. DNA was obtained from peripheral blood leukocytes of each participant. Genetic analysis included TGFBI polymerase chain reaction (PCR) amplification and automated nucleotidic sequenceing of all 17 exons of genomic DNA. Histological analysis of corneal tissue from the proband was performed after a penetrating keratoplasty. One hundred Chinese controls were scanned for the presence of the R124H mutation by amplifying TGFBI exon 4 and then by direct sequencing of PCR products.ResultsThe proband of the pedigree had phenotypic features consistent with diagnosis of ACD. He was homozygous for the same R124H mutation in TGFBI as previously reported in Japan and European countries. In addition, 4 affected and 7 unaffected individuals carried the same variation in the heterozygous state were identified. None of the 100 control subjects was positive for this mutation. Moreover, a variable expressivity and an apparent non-penetrance were observed in the individuals with heterozygous R124H mutation in our pedigree. After excluding the missed diagnosis or a late onset, it could be interpreted as a reduced penetrance.ConclusionsWe reported a novel ACD family which exhibited a reduced penetrance of phenotype in northern China. This outcome supports that although the R124H mutation is one of the genetic causes of the disease, different genetic and environmental factors may influence the expressivity and the penetrance. Uncovering the mechanism may facilitate us to inhibit the occurrence of the corneal dystrophy caused by the R124H mutation in TGFBI, irrespective of the homozygous and heterozygous mutation.

| S-EPMC2622714 | biostudies-literature

A novel phenotype-genotype correlation with an Arg555Trp mutation of TGFBI gene in Thiel-Behnke corneal dystrophy in a Chinese pedigree.

Project description:To investigate the molecular defects in a four-generation Chinese pedigree affected with Thiel-Behnke corneal dystrophy (TBCD). And to further study the relationship between genetic mutation and clinical manifestations.Individuals of the pedigree were recruited for extensive ophthalmic examinations. Histological studies of two corneal buttons obtained from lamellar keratoplasty were conducted. Peripheral blood was collected in EDTA for genomic DNA isolation from leukocytes of all affected and unaffected members. All 17 exons of the TGFBI gene were screened for mutations by polymerase chain reaction and direct DNA sequencing.Clinical examinations revealed a typical pattern of honeycomb-like TBCD. Histopathology study demonstrated eosinophilic deposits that were congo-red-positive and did not stain with periodic acid Schiff or Masson's trichrome. Genetic analysis disclosed a heterozygous p. Arg555Trp mutation resulted from a missense c. 1663C?>?T nucleotide change in exon 12 of TGFBI gene in all affected members. Morever, a second rare variant in exon 6 of the TGFBI gene (p. Arg257Trp) also cosegregated within this family and has been confirmed to be a single nucleotide polymorphism (SNP) not previously reported.The p. Arg555Trp mutation of the TGFBI gene was associated with TBCD, which revealed a novel phenotype-genotype correlation within the mutational spectrum of phenotypically diverse corneal dystrophies.

| S-EPMC4605025 | biostudies-literature

Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy.

Project description:Background/Aims:Corneal dystrophies (CDs) belong to a group of hereditary heterogeneous corneal diseases which result in visual impairment due to the progressive accumulation of deposits in different corneal layers. So far, mutations in several genes have been responsible for various CDs. The purpose of this study is to identify gene mutations in a three-generation Hui-Chinese family associated with granular corneal dystrophy type I (GCD1). Methods:A three-generation Hui-Chinese pedigree with GCD1 was recruited for this study. Slit-lamp biomicroscopy, optical coherence tomography, and confocal microscopy were performed to determine the clinical features of available members. Whole exome sequencing was performed on two patients to screen for potential disease-causing variants in the family. Sanger sequencing was used to test the variant in the family members. Results:Clinical examinations demonstrated bilaterally abundant multiple grayish-white opacities in the basal epithelial and superficial stroma layers of corneas of the two patients. Whole exome sequencing revealed that a heterozygous missense mutation (c.1663C?>?T, p.Arg555Trp) in the transforming growth factor beta-induced gene (TGFBI) was shared by the two patients, and it cosegregated with this disease in the family confirmed by Sanger sequencing. Conclusions:The results suggested that the heterozygous TGFBI c.1663C?>?T (p.Arg555Trp) mutation was responsible for GCD1 in the Hui-Chinese family, which should be of great help in genetic counseling for this family.

| S-EPMC6399521 | biostudies-literature

Genotype-phenotype correlations in Chinese patients with TGFBI gene-linked corneal dystrophy.

Project description:In this paper, we report the clinical and molecular features of the distinct TGFBI (human transforming growth factor β-induced, OMIM No. 601692) gene-linked corneal dystrophy. Altogether, five pedigrees and ten unrelated individuals diagnosed as corneal dystrophy were recruited. Peripheral venous DNA was extracted, and then amplified by polymerase chain reaction (PCR) and scanned for mutation by single-stranded conformation polymorphism (SSCP). Direct DNA sequencing was used to analyze the mutations of the TGFBI gene. In our study, thirty patients from five pedigrees and ten sporadic patients were diagnosed as four TGFBI gene-linked corneal dystrophies of granular corneal dystrophy type I (GGCD I), Avellino corneal dystrophy (ACD), lattice corneal dystrophy type I (LCD I), and lattice corneal dystrophy type IIIA (LCD IIIA), and in total, seven disease-causing mutations, namely R555W, A546D, A546T, and T538P mutations in exon 12, R124H and R124C mutations in exon 4, and P501T mutation in exon 11, were identified, while four polymorphisms of V327V, L472L, F540F, and 1665-1666insC were screened in exons 8, 11, and 12. The study ascertained the tight genotype-phenotype relationship and confirmed the clinical and genetic features of four TGFBI gene-linked corneal dystrophies.

| S-EPMC3072592 | biostudies-literature

Deterioration of Avellino corneal dystrophy in a Chinese family after LASIK.

Project description:AimTo reveal the importance of TGFBI gene screening for candidates with a family history of corneal disease or granular opacities in corneal stroma before refractive surgery.MethodsA 37-year-old male (proband) underwent bilateral laser-assisted in situ keratomileusis (LASIK) in 2002, with right vision decreased significantly in 2006. The proband and other 32 members of the family underwent a detailed ophthalmic examination, including vision acuity, intraocular pressure, slit-lamp photograph, fundus examination, optical coherence tomography (OCT) of cornea, and in vivo confocal microscope (IVCM) and peripheral blood was used for genomic DNA extraction. Seventeen TGFBI gene exons were analyzed via polymerase chain reaction amplification and direct sequencing.ResultsSlit-lamp, IVCM, and OCT images showed that a large amount of dense and confluent granular opaque were seen at the interfaces of the flap and remnant stromal bed in right and light degree in left eye. Sanger sequencing showed that there was a 371G>A mutation (CGC>CAC) in exon 4, which indicated that he harbored a heterozygote R124H mutation, identifying the diagnosis of Avellino corneal dystrophy (ACD). Among the other 32 family members, 6 of them harbored the identical mutation to that in the proband.ConclusionACD will worsen and recur after LASIK. Preoperative gene-screening for TGFBI mutations is important in diagnosing ACD.

| S-EPMC8165627 | biostudies-literature

A novel mutation I522N within the TGFBI gene caused lattice corneal dystrophy I.

Project description:PurposeTo identify mutations within the TGFBI gene in a Chinese family with lattice corneal dystrophy type I (LCD I).MethodsGenomic DNA of three affected, four unaffected family members and 50 normal individuals was extracted from peripheral leukocytes. All exons of TGFBI were amplified by polymerase chain reaction (PCR) methods and direct sequencing was carried out for mutation analysis.ResultsA missense mutation (1565T-->A) in exon12 of TGFBI led to an amino acid substitution I522N in the TGFB-induced protein in all affected family members, but the mutation was not detected in normal subjects of the family and control individuals.ConclusionsWe conclude that the novel mutation I522N causes lattice corneal dystrophy type I in the studied family. This is the first report of the I522N mutation within TGFBI in LCD I worldwide.

| S-EPMC2786890 | biostudies-literature

TGFBI and CHST6 gene analysis in Chinese stromal corneal dystrophies.

Project description:AimTo investigate whether mutations in TGFBI gene or CHST6 gene correlated with stromal corneal dystrophies (CD) in 8 Chinese probands.MethodsEight 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.ResultsThree 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.ConclusionWithin 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, GCD II), 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.

| S-EPMC3388397 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data