Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to chromosome Iq.

ABSTRACT: A large Caucasian family is presented, in which a juvenile-onset form of open-angle glaucoma is transmitted in an autosomal dominant fashion. Sixteen affected family members were identified from 31 at-risk individuals descended from the affected founder. Affected patients developed high intraocular pressures (sometimes > 40 mm Hg) within the first 2 decades of life. Linkage analysis between the disease phenotype and 12 microsatellite repeat markers located on chromosome 1q gave a maximum lod score of 8.38 at a recombination fraction of zero for marker D1S210. Analysis of recombinant haplotypes suggests a total inclusion region of about 14 cM between markers D1S194 and D1S218 at 1q21-q31. This represents the second juvenile-glaucoma family, in which the disease has been mapped to the long arm of chromosome 1.

SUBMITTER: Richards JE

PROVIDER: S-EPMC1918066 | biostudies-other | 1994 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to chromosome Iq.

Richards J E JE Lichter P R PR Boehnke M M Uro J L JL Torrez D D Wong D D Johnson A T AT

American journal of human genetics 19940101 1

A large Caucasian family is presented, in which a juvenile-onset form of open-angle glaucoma is transmitted in an autosomal dominant fashion. Sixteen affected family members were identified from 31 at-risk individuals descended from the affected founder. Affected patients developed high intraocular pressures (sometimes > 40 mm Hg) within the first 2 decades of life. Linkage analysis between the disease phenotype and 12 microsatellite repeat markers located on chromosome 1q gave a maximum lod sco ...[more]

PMID: 8279471

Similar Datasets

A genome-wide scan maps a novel autosomal dominant juvenile-onset open-angle glaucoma locus to 2p15-16.

Project description:PurposeTo study the clinical features and to perform genetic linkage study in two large Chinese families with autosomal dominant juvenile-onset primary open-angle glaucoma (POAG).MethodsEighteen members of one Chinese family and 25 members of a second Chinese family with juvenile-onset primary open-angle glaucoma (POAG) were investigated. Thirteen members in one family and 14 members in the second family were diagnosed with juvenile-onset POAG. A genome-wide linkage scan was performed on one family using 411 short tandem repeat (STR) markers. Subsequent fine mapping was performed in the two study families using a modified fluorescent labeled M13 primer method.ResultsA whole genome-wide scan in one family showed linkage to chromosome 2p15-p16 with a two-point maximum LOD score of 5.01 at theta=0 between the disease phenotype and STR marker D2S337. The second family was also mapped to the same locus with a two-point maximum LOD score of 6.30 at theta=0 for D2S378. Haplotype analysis in these two families demonstrated that they shared the same disease haplotype, suggesting they have inherited the mutation from a common founder. The maximum LOD scores were 8.93 at theta=0 for D2S378 and 9.9 at theta=0 for D2S337 when the two families were combined for analysis. The disease interval for these two families was localized to 9.2 cM or 13.3 Mb between D2S123 and D2S2397. There are 42 known genes/transcripts within the interval. Five of these genes were sequenced, and no disease-causing mutation was identified in either family.ConclusionsThis novel juvenile-onset POAG locus on chromosome 2p15-16 is overlapped by the Glaucoma 1, open angle, H (GLC1H) locus for adult-onset POAG. Eventual identification of the disease-causing gene will provide insights into the pathogenesis of POAG.

| S-EPMC2324117 | biostudies-literature

Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q.

Project description:Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C.

| S-EPMC1712411 | biostudies-other

Mutations in the CYP1B1 gene may contribute to juvenile-onset open-angle glaucoma.

Project description:PURPOSE: Glaucoma is one of the leading causes of blindness in the world. Juvenile-onset open-angle is a subtype of glaucoma. In this context, we investigate the possible mutations in the promoter and coding regions of the CYP1B1 gene among patients suffering juvenile-onset open-angle glaucoma (JOAG). METHODS: The CYP1B1 gene was analysed for mutations in 61 unrelated Taiwanese probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted from peripheral blood leukocytes and then subjected to PCR. The amplified products were screened for base mutations by autosequence. Next, data from the two groups were compared using the ?(2) test. Additionally, three-dimensional (3D) modelling of the human wild-type and p.R390H mutation was performed using SWISS-MODEL, an automated homology modelling program. Finally, the figure was prepared for the modelled structures by using the Accelrys ViewerLite 5.0 program. RESULTS: Analysis results indicated two CYP1B1 mutations and five polymorphisms. The prevalence of CYP1B1 gene mutations in this study was 4.92% (3/61). The mutations included a missense mutation (p.Arg390His; 2/3) and a mutation in the 5'-untranslated region (c.1-313A>C; 1/3). Moreover, computer-assisted modelling revealed that this p.R390H mutation affects the intra-molecular interaction in the hydrogen-bonding interaction with Glu387 and Asn428, thus altering significantly the efficiency of the haem-binding and proper folding of the molecule. CONCLUSIONS: As a result, the p.Arg390His mutation might affect the protein structure and, ultimately, the normal function of CYP1B1. Therefore, we suggest that the c.1169G>A (p.Arg390His) mutation of CYP1B1 may be a risk factor for the development of JOAG.

| S-EPMC3470042 | biostudies-literature

Pro370Leu myocilin mutation in a Chinese pedigree with juvenile-onset open angle glaucoma.

Project description:PurposeTo investigate the genotype and phenotype of juvenile-onset open angle glaucoma (JOAG) in a Chinese family (PN pedigree).MethodsEach family member was comprehensively examined by an experienced ophthalmologist. The clinical characteristics of the family patients with JOAG were documented. Blood samples were obtained from 22 available participants from the PN pedigree. Linkage analysis was performed to identify the possible chromosome loci. The presence of gene mutation was ascertained by polymerase chain reaction amplification and subsequent direct sequencing.ResultsThe affected members in the PN pedigree are characterized by early age of onset (mean age at diagnosis is 17 years old), severe clinical presentations, high intraocular pressure (mean IOP of 34.18±2.97 mmHg), and poor response to pharmacological treatment (87.5% of the patients required filtering surgery). The region on chromosome 1 between D1S3464 and D1S1619 was identified in this pedigree by linkage analysis. A Pro370Leu myocilin mutation resulting from a heterozygous C→T transition at the 1,109th nucleotide in exon 3 was detected by gene sequencing. The Pro370Leu mutation co-segregated among all affected individuals of PN pedigree.ConclusionsThe GLC1A Pro370Leu mutation is firmly correlated with a severe POAG phenotype. These data provide clues for the severe disease-causing nature of the Pro370Leu allele. Gene screening may be a useful method for pre-symptom diagnosis and a forewarning to detect the at-risk individuals in familial open-angle glaucoma patients, especially in pedigrees of early-onset.

| S-EPMC3110496 | biostudies-literature

Autosomal dominant nanophthalmos (NNO1) with high hyperopia and angle-closure glaucoma maps to chromosome 11.

Project description:Nanophthalmos is an uncommon developmental ocular disorder characterized by a small eye, as indicated by short axial length, high hyperopia (severe farsightedness), high lens/eye volume ratio, and a high incidence of angle-closure glaucoma. We performed clinical and genetic evaluations of members of a large family in which nanophthalmos is transmitted in an autosomal dominant manner. Ocular examinations of 22 affected family members revealed high hyperopia (range +7.25-+13.00 diopters; mean +9.88 diopters) and short axial length (range 17.55-19.28 mm; mean 18.13 mm). Twelve affected family members had angle-closure glaucoma or occludable anterior-chamber angles. Linkage analysis of a genome scan demonstrated highly significant evidence that nanophthalmos in this family is the result of a defect in a previously unidentified locus (NNO1) on chromosome 11. The gene was localized to a 14.7-cM interval between D11S905 and D11S987, with a maximum LOD score of 5. 92 at a recombination fraction of .00 for marker D11S903 and a multipoint maximum LOD score of 6.31 for marker D11S1313. NNO1 is the first human locus associated with nanophthalmos or with an angle-closure glaucoma phenotype, and the identification of the NNO1 locus is the first step toward the cloning of the gene. A cloned copy of the gene will enable examination of the relationship, if any, between nanophthalmos and less severe forms of hyperopia and between nanophthalmos and other conditions in which angle-closure glaucoma is a feature.

| S-EPMC1377551 | biostudies-other

Absence of optineurin (OPTN) gene mutations in Taiwanese patients with juvenile-onset open-angle glaucoma.

Project description:PurposeTo investigate sequence variants in the optineurin (OPTN) gene in patients with juvenile-onset open-angle glaucoma (JOAG) in Taiwan.MethodsWe analyzed the sequence variants of OPTN in 51 unrelated Taiwanese probands with JOAG and in 51 control group subjects who did not have JOAG. Genomic DNA was extracted from the individuals and subjected to polymerase chain reaction (PCR) to amplify all 16 exons and flanking introns of OPTN. The amplified products were then screened for base variants by autosequence. Data from the two study groups were then compared using Fisher's exact test and Armitage's trend test.ResultsFifteen variants of OPTN were found in the 51 JOAG patients and 51 unrelated normal controls. Two were missense variants (M98K and K322E), one was a synonymous codon change (T34T), and 12 were changes in the noncoding sequences. Seven of the variants have been reported and eight were novel. All of the sequence changes were found in patients with JOAG and in the normal controls except for variant c.-233+25C>G, which was found only in the control group. Allelic frequencies of these sequence changes did not differ significantly between patients and controls (p>0.05) except for the variant c.-233+25C>G (p<0.001). Genotype frequencies of c.-233+25C>G was shown to be significant between the two groups using Fisher's two-tailed exact test (p<0.001) and Armitage's trend test (p=6.815e(-06)).ConclusionsOur data indicate that none of the mutations in OPTN are associated with JOAG. The variant M98K is not a risk factor and the variant c.-233+25C>G may be protective against glaucoma in Taiwanese.

| S-EPMC2268851 | biostudies-literature

Screening of CYP1B1 Arg368His as predominant mutation in North Indian primary open angle glaucoma and juvenile onset glaucoma patients.

Project description:In India, mutations in Cytochrome P450 (CYP1B1) are a predominant cause of not only primary congenital glaucoma (PCG) but also involved in primary open angle glaucoma (POAG) and juvenile onset glaucoma (JOAG). After ethical clearance, 100 POAG patients, 30 primary angle closure glaucoma (PACG) patients and 130 ethnically matched controls were recruited in this study. Genomic DNA was isolated from the blood and screened for p.Arg368His mutation in CYP1B1 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). On PCR-RFLP, 10/100 cases (10%) were found positive for Arg368His mutation. In North Indian POAG cases studied, p.Arg368His mutation was found only in heterozygous state. The frequency of p.Arg368His CYP1B1 mutation in heterozygote state (10.0%) observed in our study in North Indian POAG patients is the highest in comparison to frequency observed in other ethnic groups from Southern and Eastern India.

| S-EPMC6363938 | biostudies-literature

An Application of NGS for WDR36 Gene in Taiwanese Patients with Juvenile-Onset Open-Angle Glaucoma.

Project description:Primary open-angle glaucoma (POAG) is one of the most important disease in ophthalmology with high prevalence and risk of irreversible blindness. If diagnosed before the age of 35, it is usually categorized as juvenile open-angle glaucoma (JOAG). The WDR36 gene is reckoned as one of the major causative genes of POAG, and had been studied to be related to the pathogenesis of POAG in the literature. We have selected 61 JOAG patients and 61 JOAG-free individuals, and by next-generation sequencing method, the WDR36 gene of the subjects were analyzed. We identified 26 variations exclusively in JOAG group. Among these 26 variations, there were 3 noteworthy variations. First, a novel variation c.460-650A>G was found in our study which might cause premature termination of splicing of the conserved domain in WDR36; second, c.1494+1111G>T (rs13178997) had significantly different frequency in our JOAG patients compared to the reference frequency on NCBI; third, a variation c.710+30C>T (rs10038177) was found in our study, which had already been reported to be related to high-pressure glaucoma. We offer the profile of WDR36 in JOAG in Taiwan population, and we suggest that WDR36 gene is involved in the pathogenesis of JOAG as a subordinate modifier gene.

| S-EPMC5666558 | biostudies-literature

Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset open angle glaucoma.

Project description:PurposeTo describe the clinical and genetic findings in one Chinese family with juvenile-onset open angle glaucoma (JOAG).MethodsOne family was examined clinically and a follow-up took place 5 years later. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Linkage analysis was performed with three microsatellite markers around the MYOC gene (D1S196, D1S2815, and D1S218) in the family. Mutation screening of all coding exons of MYOC was performed by direct sequencing of PCR-amplified DNA fragments and restriction fragment length polymorphism (RFLP) analysis. Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted the effects of variants detected on secondary structures of the MYOC protein.ResultsClinical examination and pedigree analysis revealed a three- generation family with seven members diagnosed with JOAG, three with ocular hypertension, and five normal individuals. Through genotyping, the pedigree showed a linkage to the MYOC on chromosome 1q24-25. Mutation screening of MYOC in this family revealed an A-->T transition at position 1348 (p. N450Y) of the cDNA sequence. This missense mutation co-segregated with the disease phenotype of the family, but was not found in 100 normal controls. Secondary structure prediction of the p.N450Y by the GOR method revealed the replacement of a coil with a beta sheet at the amino acid 447.ConclusionsEarly onset JOAG, with incomplete penetrance, is consistent with a novel mutation in MYOC. The finding provides pre-symptomatic molecular diagnosis for the members of this family and is useful for further genetic consultation.

| S-EPMC2927375 | biostudies-literature

Fine mapping of the GLC1K juvenile primary open-angle glaucoma locus and exclusion of candidate genes.

Project description:PurposePrimary open-angle glaucoma is a leading cause of blindness worldwide. We previously identified a region on chromosome 20p12 associated with juvenile-onset primary open-angle glaucoma (JOAG) that was designated GLC1K. The aim of this study is to refine the boundaries of the GLC1K region and to screen selected candidate genes located within the refined region for biologically significant mutations.MethodsFour JOAG families (44 individuals) with linkage to GLC1K were used for this study. Informative single nucleotide polymorphism (SNP) markers located throughout the previously defined region were used for haplotype analysis. Four candidate genes within the refined region were screened for biologically significant mutations using direct genomic sequencing: bone morphogenetic protein 2 (BMP2); phospholipase C beta 1 (PLCB1); phospholipase C beta 4 (PLCB4); and BTB POZ domain containing 3 (BTBD3).ResultsHaplotype analysis identified a new critical interval of 12.7 Mb using a combination of SNPs and microsatellite markers. This analysis extended the region of GLC1K from D20S846 to rs6081603 in affected individuals, and the region was further reduced to 9 Mb if unaffected recombinant individuals were included in the analysis. Biologically significant DNA sequence variants were not identified in the BMP2, PLCB1, PLCB4, or BTBD3 genes in these families.ConclusionsUsing recombinant breakpoint mapping and haplotypes based on a combination of SNP and microsatellite markers, the GLC1K region has been reduced to a maximum of 12.7 Mb and a minimum of 9 Mb. Four genes that are located within the refined region with attractive ocular expression and function have been excluded as causative genes for JOAG.

| S-EPMC2480480 | 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