Browse
Submit Data
Databases
API
Help

Dataset Information

89 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Novel CRYBB2 Stopgain Mutation Causing Congenital Autosomal Dominant Cataract in a Chinese Family.

ABSTRACT: Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples. After the whole exome sequencing data were filtered through a series of existing variation databases, a heterozygous mutation c.499T

SUBMITTER: Zhou Y

PROVIDER: S-EPMC5153472 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A Novel <i>CRYBB2</i> Stopgain Mutation Causing Congenital Autosomal Dominant Cataract in a Chinese Family.

Zhou Yu Y Zhai Yaru Y Huang Lulin L Gong Bo B Li Jie J Hao Fang F Wu Zhengzheng Z Shi Yi Y Yang Yin Y

Journal of ophthalmology 20161129

Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was perf ...[more]

PMID: 28025620

Similar Datasets

A novel GJA8 mutation (p.I31T) causing autosomal dominant congenital cataract in a Chinese family.

Project description:PURPOSE: To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family. METHODS: Family history and clinical data were recorded. The genomic DNA was extracted from peripheral blood leukocytes. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point logarithm of odds (LOD) scores were calculated by using the Linkage software after genotyping. Mutations were detected by DNA sequence analysis of the candidate genes. Effects of amino acid changes on the structure and function of proteins were predicted by bioinformatics analysis. RESULTS: Evidence of a linkage was obtained at markers D1S514 (LOD score [Z]=3.48, recombination fraction [theta]=0.0) and D1S1595 (Z=2.49, theta=0.0). Haplotype analysis indicated that the cataract gene was close to these two markers. Sequencing of the connexin 50 (GJA8) gene revealed a T>C transition at nucleotide position c.92. This nucleotide change resulted in the substitution of highly conserved isoleucine by threonine at codon 31(I31T). This mutation co-segregated with all affected individuals and was not observed in unaffected or 110 normal unrelated individuals. Bioinformatics analysis showed that a highly conserved region was located at Ile31, and the mutation was predicted to affect the function and secondary structure of the GJA8 protein. CONCLUSION: A novel mutation in GJA8 was detected in a Chinese family with autosomal dominant congenital nuclear cataract, providing clear evidence of a relationship between the genotype and the corresponding cataract phenotype.

| S-EPMC2794658 | biostudies-literature

A novel CRYGD mutation (p.Trp43Arg) causing autosomal dominant congenital cataract in a Chinese family.

Project description:To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family, molecular genetic investigation via haplotype analysis and direct sequencing were performed Sequencing of the CRYGD gene revealed a c.127T>C transition, which resulted in a substitution of a highly conserved tryptophan with arginine at codon 43 (p.Trp43Arg). This mutation co-segregated with all affected individuals and was not observed in either unaffected family members or in 200 normal unrelated individuals. Biophysical studies indicated that the p.Trp43Arg mutation resulted in significant tertiary structural changes. The mutant protein was much less stable than the wild-type protein, and was more prone to aggregate when subjected to environmental stresses such as heat and UV irradiation.

| S-EPMC3035819 | biostudies-literature

Characterization of a novel mutation in the CRYBB2 gene associated with autosomal dominant congenital posterior subcapsular cataract in a Chinese family.

Project description:PURPOSE: To identify the underlying genetic defect in four generations of a Chinese family affected with bilateral congenital posterior subcapsular cataracts. METHODS: Clinical data from patients in the family were recorded by slit-lamp photography. Genomic DNA samples were extracted from peripheral blood of the pedigree members. Mutation screening was performed in the candidate gene by bidirectional sequencing of the amplified products. The mutation was verified by restriction fragment length polymorphism (RFLP) analysis. RESULTS: The congenital cataract phenotype of the pedigree was identified as posterior subcapsular by slit-lamp photography. Sequencing of the candidate genes detected a heterozygous c.5C?T change in the coding region of the ?B2-crystallin gene (CRYBB2), resulting in the substitution of a highly conserved alanine to valine (p. A2V). All nine family members affected with cataracts were positive for this change, but it was not observed in any of the unaffected members of the family. The transition resulted in the loss of a HaeIII restriction site in the affected members of the pedigree, which was present in the unaffected family members and in all of the 100 unrelated individuals tested. CONCLUSIONS: This study has identified a novel CRYBB2 gene mutation, resulting in the amino substitution p. A2V in a Chinese family with posterior subcapsular congenital cataracts. This mutation is probably the causative lesion for the observed phenotype in this family.

| S-EPMC3021577 | biostudies-literature

A novel GJA8 mutation (p.V44A) causing autosomal dominant congenital cataract.

Project description:PurposeTo examine the mechanism by which a novel connexin 50 (Cx50) mutation, Cx50 V44A, in a Chinese family causes suture-sparing autosomal dominant congenital nuclear cataracts.MethodsFamily history and clinical data were recorded and direct gene sequencing was used to identify the disease-causing mutation. The Cx50 gene was cloned from a human lens cDNA library. Connexin protein distributions were assessed by fluorescence microscopy. Hemichannel functions were analyzed by dye uptake assay. Formation of functional channels was assessed by dye transfer experiments.ResultsDirect sequencing of the candidate GJA8 gene revealed a novel c.131T>C transition in exon 2, which cosegregated with the disease in the family and resulted in the substitution of a valine residue with alanine at codon 44 (p. V44A) in the extracellular loop 1 of the Cx50 protein. Both Cx50 and Cx50V44A formed functional gap junctions, as shown by the neurobiotin transfer assay. However, unlike wild-type Cx50, Cx50V44A was unable to form open hemichannels in dye uptake experiments.ConclusionThis work identified a unique congenital cataract in the Chinese population, caused by the novel mutation Cx50V44A, and it showed that the V44A mutation specifically impairs the gating of the hemichannels but not the gap junction channels. The dysfunctional hemichannels resulted in the development of human congenital cataracts.

| S-EPMC4269439 | biostudies-literature

A nonsense mutation in CRYGC associated with autosomal dominant congenital nuclear cataract in a Chinese family.

Project description:PURPOSE: To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family. METHODS: Family history and phenotypic data were recorded, and the phenotypes were documented by slit lamp photography. The genomic DNA was extracted from peripheral blood leukocytes. All the exons and flanking intronic sequences of CRYGC and CRYGD were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structural models of the wild type and mutant gammaC-crystallin were generated and analyzed by SWISS-MODEL. RESULTS: Sequencing of the coding regions of CRYGC and CRYGD showed the presence of a heterozygous C>A transversion at c.327 of the coding sequence in exon 3 of CRYGC (c.327C>A), which results in the substitution of a wild type cysteine to a nonsense codon (C109X). One and a half Greek key motifs at the COOH-terminus were found to be absent in the structural model of the mutant truncated gammaC-crystallin. CONCLUSIONS: A novel nonsense mutation in CRYGC was detected in a Chinese family with consistent autosomal dominant congenital nuclear cataract, providing clear evidence of a relationship between the genotype and the corresponding cataract phenotype.

| S-EPMC2447816 | biostudies-literature

A novel mutation in γD-crystallin associated with autosomal dominant congenital cataract in a Chinese family.

Project description:PurposeTo identify the pathogenic gene mutation in a Chinese family with autosomal dominant congenital nuclear cataract.MethodsAfter obtaining informed consent, detailed ophthalmic examinations were performed and genomic DNAs were obtained from eleven family members in a three-generation Chinese family with five affected. All exons of candidate genes associated with congenital nuclear cataract were amplified by polymerase chain reaction (PCR) and the PCR products were sequenced in both directions. The hydrophobic property of the mutant protein was analyzed with bioinformatics program ProtScale. The structure homology modeling of the mutant protein was based on Swiss-Model Serve, and its structure was displayed and compared with native γD-crystallin (CRYGD) using the RasMol software.ResultsBy sequencing the encoding regions of the candidate genes, a novel mutation (c.110G>C) was detected in exon 2 of CRYGD, which resulted in the substitution of a highly conserved arginine by proline at codon 36 (p.R36P). The mutation co-segregated with all patients and was absent in 100 normal Chinese controls. Bioinformatics analysis showed an obvious increase of the local hydrophilicity of the R36P mutant γD-crystallin. The homology modeling showed that the structure of the mutant protein was similar with that of native human γD-crystallin.ConclusionsThe study identified a novel mutation (c. 110G>C) in CRYGD associated with autosomal dominant congenital cataract in a Chinese family. It expands the mutation spectrum of CRYGD in association with congenital cataract.

| S-EPMC3081795 | biostudies-literature

A novel mutation in CRYAB associated with autosomal dominant congenital nuclear cataract in a Chinese family.

Project description:PurposeTo identify the genetic defects associated with autosomal dominant congenital nuclear cataract in a Chinese family.MethodsClinical data were collected, and the phenotypes of the affected members in this family were recorded by slit-lamp photography. Genomic DNA was isolated from peripheral blood. Mutations were screened in cataract-associated candidate genes through polymerase chain reaction (PCR) analyses and sequencing. Structural models of the wild-type and mutant alphaB-crystallin were generated and analyzed by SWISS-MODEL.ResultsMutation screening identified only one heterozygous G-->A transition at nucleotide 32 in the first exon of alphaB-crystallin (CRYAB), resulting in an amino acid change from arginine to histidine at codon 11 (R11H). This mutation segregated in all available affected family members but was not observed in any of the unaffected persons of the family. The putative mutation disrupted a restriction site for the enzyme, Fnu4HI, in the affected family members. The disruption, however, was not found in any of the randomly selected ophthalmologically normal individuals or in 40 unrelated senile cataract patients. Computer-assisted prediction suggested that this mutation affected the biochemical properties as well as the structure of alphaB-crystallin.ConclusionsThese results supported the idea that the novel R11H mutation was responsible for the autosomal dominant nuclear congenital cataract in this pedigree.

| S-EPMC2709425 | biostudies-literature

A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family.

Project description:BackgroundAlmost one-third of congenital cataracts are primarily autosomal dominant disorders, which are also called autosomal dominant congenital cataract, resulting in blindness and clouding of the lens. The purpose of this study was to identify the disease-causing mutation in a Chinese family affected by bilateral, autosomal dominant congenital cataract.MethodsThe detection of candidate gene mutation and the linkage analysis of microsatellite markers were performed for the known candidate genes. Molecular mapping and cloning of candidate genes were used in all affected family members to screen for potential genetic mutations and the mutation was confirmed by single enzyme digestion.ResultsThe proband was diagnosed with isolated, congenital cataract without the typical clinical manifestations of cataract, which include diabetes, porencephaly, sporadic intracerebral hemorrhage, and glomerulopathy. A novel mutation, c.2345 G > C (Gly782Ala), in exon 31 of the collagen type IV αlpha1 (COL4A1) gene, which encodes the collagen alpha-1(IV) chain, was found to be associated with autosomal dominant congenital cataract in a Chinese family. This mutation was not found in unaffected family members or in 200 unrelated controls. Sequence analysis confirmed that the Gly782 amino acid residue is highly conserved.ConclusionsThe novel mutation (c.2345 G > C) of the COL4A1 gene is the first report of a non-syndromic, autosomal dominant congenital cataract, thereby highlighting the important role of type IV collagen in the physiological and optical properties of the lens.

| S-EPMC4236509 | biostudies-literature

Whole Exome Sequencing Reveals a Mutation in CRYBB2 in a Large Mexican Family with Autosomal Dominant Pulverulent Cataract.

Project description:Congenital cataract, an important cause of reversible blindness, is due to several causes including Mendelian inheritance. Thirty percent of cataracts are hereditary with participation of the gamma crystallin genes. Clinical and genetic heterogeneity is observed in patients with gene mutations and congenital cataract; about 40 genetic loci have been associated with hereditary cataract. In this study, we identified the underlying genetic cause of an autosomal dominant pulverulent cataract (ADPC) in a large Mexican family. Twenty-one affected patients and 20 healthy members of a family with ADPC were included. Genomic DNA was analyzed by whole exome sequencing in the proband, a normal daughter, and in an affected son, whereas DNA Sanger sequencing was performed in all members of the family. After the bioinformatics analysis, all samples were genotyped using Sanger sequencing to eliminate variants that do not cosegregate with the cataract. We observed a perfect cosegregation of a nonsense mutation c.475C>T (p.Q155*) in exon 6 of the CRYBB2 gene with ADPC. We calculated a logarithm of the odds score of 5.5. This mutation was not detected in healthy members of the family and in 100 normal controls. This is the first Mexican family with ADPC associated with a p.Q155* mutation. Interestingly, this specific mutation in the CRYBB2 gene seems to be exclusively associated with pulverulent/cerulean cataract (with some clinical variability) independent of the population's genetic background.

| S-EPMC4906430 | biostudies-literature

A novel beaded filament structural protein 1 (BFSP1) gene mutation associated with autosomal dominant congenital cataract in a Chinese family.

Project description:PURPOSE: To identify the disease-causing mutation in a five-generation Chinese family affected with bilateral congenital nuclear cataract. METHODS: Linkage analysis was performed for the known candidate genes and whole-exome sequencing was used in two affected family members to screen for potential genetic mutations; Sanger sequencing was used to verify the mutations throughout family. RESULTS: A novel beaded filament structural protein 1 (BFSP1) gene missense mutation was identified. Direct sequencing revealed a heterozygous G>A transversion at c.1042 of the coding sequence in exon 7 of BFSP1 (c.1042G>A) in all affected members, which resulted in the substitution of a wild-type aspartate to an asparagine (D348N). This mutation was neither seen in unaffected family members nor in 200 unrelated people as controls. CONCLUSIONS: A novel mutation (c.1042G>A) at exon 7 of BFSP1, which creates a substitution of an aspartate to an asparagine (p.D348N) was identified to be associated with autosomal dominant congenital cataract in a Chinese family. This is the first report of autosomal dominant congenital cataract being associated with a mutation in BFSP1, highlighting the important role of BFSP1 for physiological lens function and optical properties.

| S-EPMC3874047 | 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