A Glaucoma Case-control Study of the WDR36 Gene D658G sequence variant.

Purpose: To investigate in Australian patients with glaucoma and normal controls the prevalence and associated phenotype of the WDR36 D658G mutation, which has previously been suggested to be a disease-causing mutation in pedigrees with primary open-angle glaucoma (POAG).

Design: Case-control study.

Methods: Two hundred forty-nine individuals with POAG and 217 age-matched control subjects were recruited through the Glaucoma Inheritance Study in Tasmania, Australia.

Complex genetics of complex traits: the case of primary open-angle glaucoma.

Glaucoma, which is a complex heterogeneous disease, presents an ideal case for genetic investigation. Primary open-angle glaucoma (POAG) is the commonest subtype and will be the focus of this review. When detected early, POAG is amenable to therapeutic intervention.

Disease severity of familial glaucoma compared with sporadic glaucoma.

Objective: To determine whether there is a difference in disease severity between familial and sporadic primary open-angle glaucoma (POAG).

Methods: A cross-sectional study design compared the distribution of Glaucoma Inheritance Study in Tasmania (GIST) severity scores of patients with genealogically confirmed familial POAG and those with sporadic POAG. The GIST severity scores provide a combined weighting of glaucoma severity based on findings from visual field defects and optic disc analysis, with and without intraocular pressure.

Innate immunity in plants: a continuum of layered defenses.

Plant responses to pathogenic invaders result from recognition of nonself elicitors. Host surveillance proteins activate distinct signaling pathways that induce partially overlapping defensive responses. Pathogen virulence is promoted by inhibition of these pathways.

Nance-Horan syndrome protein, NHS, associates with epithelial cell junctions.

Nance-Horan syndrome, characterized by congenital cataracts, craniofacial, dental abnormalities and mental disturbances, is an X-linked disorder with significant phenotypic heterogeneity. Affected individuals have mutations in the NHS (Nance-Horan syndrome) gene typically resulting in premature truncation of the protein. This report underlines the complexity of the regulation of the NHS gene that transcribes several isoforms.

2005 Gregg Lecture: Congenital cataract--from rubella to genetics.

On the 65th anniversary of Gregg's observation "Congenital cataract following German measles in the mother", rubella has retired as the leading cause of congenital cataract, from 87% of Gregg's cohort to less than 3% over the last 25 years and almost zero now in Australia and other developed countries. However, people must keep vigilance in maintaining immunization rates and encourage immunization in developing countries. At least one-fifth of congenital cataract is familial.

The PITX3 gene in posterior polar congenital cataract in Australia.

Purpose: Congenital cataract is a significant cause of blindness worldwide. Many genes are known to cause the disorder. A large multigenerational pedigree was investigated for the genetic cause of a posterior polar autosomal dominant congenital cataract.

A myocilin Gln368STOP homozygote does not exhibit a more severe glaucoma phenotype than heterozygous cases.

Purpose: To describe the phenotype of an individual homozygous for the common Gln368STOP myocilin mutation and to discuss the other family members.

Design: Cascade screening was performed for Australian families that had been identified as having the myocilin Gln368STOP mutation.

Methods: Recruited subjects underwent comprehensive clinical examination and mutation analysis for the Gln368STOP myocilin mutation by direct sequencing.

A large GLC1C Greek family with a myocilin T377M mutation: inheritance and phenotypic variability.

Purpose: POAG is a complex disease; therefore, families in which a glaucoma gene has been mapped may carry additional POAG genes. The goal of this study was to determine whether mutations in the myocilin (MYOC) gene on chromosome 1 are present in two POAG families, which have previously been mapped to the GLC1C locus on chromosome 3.

Methods: The three exons of MYOC were screened by denaturing (d)HPLC.

Confirmation of the adult-onset primary open angle glaucoma locus GLC1B at 2cen-q13 in an Australian family.

Primary open-angle glaucoma (POAG) is genetically heterogeneous, with 6 named POAG loci GLC1A-F mapped and genes myocilin (MYOC) and optineurin (OPTN) identified at 2 of the loci. Using penetrance-model-free methods, we screened the POAG loci GLC1A-F in an extended Australian pedigree, using 3-5 markers within each locus. p values of less than 0.

Mutations in TCF8 cause posterior polymorphous corneal dystrophy and ectopic expression of COL4A3 by corneal endothelial cells.

Posterior polymorphous corneal dystrophy (PPCD, also known as PPMD) is a rare disease involving metaplasia and overgrowth of corneal endothelial cells. In patients with PPCD, these cells manifest in an epithelial morphology and gene expression pattern, produce an aberrant basement membrane, and, sometimes, spread over the iris and nearby structures in a way that increases the risk for glaucoma. We previously mapped PPCD to a region (PPCD3) on chromosome 10 containing the gene that encodes the two-handed zinc-finger homeodomain transcription factor TCF8.

A common disease haplotype for the Q368STOP mutation of the myocilin gene in Australian and Canadian glaucoma families.

Purpose: To ascertain whether there is a common disease haplotype for the Q368STOP mutation of the myocilin gene in Australian and Canadian families with primary open-angle glaucoma (POAG).

Design: Family pedigree study.

Methods: A disease haplotype for the Q368STOP mutation of the myocilin gene has previously been identified in 15 Tasmanian families with POAG.

Linkage to 10q22 for maximum intraocular pressure and 1p32 for maximum cup-to-disc ratio in an extended primary open-angle glaucoma pedigree.

Purpose: The purpose of this study was to identify genetic contributions to primary open-angle glaucoma (POAG) through investigations of two quantitative components of the POAG phenotype.

Methods: Genome-wide multipoint variance-components linkage analyses of maximum recorded intraocular pressure (IOP) and maximum vertical cup-to-disc ratio were conducted on data from a single, large Australian POAG pedigree that has been found to segregate the myocilin Q368X mutation in some individuals.

Results: Multipoint linkage analysis of maximum recorded IOP produced a peak LOD score of 3.

Central corneal thickness is highly heritable: the twin eye studies.

Purpose: A classic twin study was performed to determine the heritability of central corneal thickness (CCT), an important parameter in glaucoma assessment.

Methods: The concordance of CCT between monozygotic (MZ) and dizygotic (DZ) twins was compared. A total of 256 twin pairs (131 MZ and 125 DZ) were recruited from three centers: the Twin Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Twins U.

Post-cycloplegia myopic shift in an older population.

Purpose: To demonstrate that use of a mydriatic agent remains a significant confounder in autorefraction of the presbyopic population.

Methods: The pre- and post-cycloplegic autorefraction results of 37 subjects over 50 years of age were measured using a Humphrey-598 autorefractor. The results of both eyes were included in a multivariate regression analysis.

The Q368STOP myocilin mutation in a population-based cohort: the Blue Mountains Eye Study.

Purpose: To investigate the prevalence of the Q368STOP myocilin mutation in a population-based cohort: the Blue Mountains Eye Study (BMES).

Design: Population-based study.

Methods: DNA was extracted from 2,142 individuals collected through the BMES, including 31 individuals with glaucoma.

Two Pseudomonas syringae type III effectors inhibit RIN4-regulated basal defense in Arabidopsis.

Plant cells have two defense systems that detect bacterial pathogens. One is a basal defense system that recognizes complex pathogen-associated molecular patterns (PAMPs). A second system uses disease-resistance (R) proteins to recognize type lll effector proteins that are delivered into the plant cell by the pathogen's type III secretion system.

Genotypic and phenotypic spectrum of X-linked retinoschisis in Australia.

Background: X-linked retinoschisis (XLRS), an X-linked recessive inherited degenerative retinopathy, is characterized by splitting in the nerve fibre layer and is caused by alterations in the RS1 gene. The aim of the present study was to review both the phenotypic features of XLRS and the mutation spectrum of the RS1 gene in an Australian cohort.

Methods: Patients were recruited from ophthalmic and paediatric hospitals as well as private ophthalmic clinics across Australia.

Evidence for a novel glaucoma locus at chromosome 3p21-22.

Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the world. It is a clinically variable group of diseases with the majority of cases presenting as the late onset adult type. Several chromosomal loci have been implicated in disease aetiology, but causal mutations have only been identified in a small proportion of glaucoma.

Chromosomal abnormalities and glaucoma: a case of congenital glaucoma with trisomy 8q22-qter/ monosomy 9p23-pter.

Purpose: To present a case of congenital glaucoma with an unbalanced translocation trisomy 8q22-qter/monosomy 9p23-pter, resulting in trisomy of the GLC1D locus. To perform a literature review of chromosomal abnormalities associated with glaucoma.

Method: A case report of a family with balanced translocation without glaucoma and unbalanced translocation with congenital glaucoma.

Are Duane syndrome and infantile esotropia allelic?

Purpose: To evaluate the clinical overlap of families with Duane syndrome and infantile esotropia to determine whether the identification of genes for Duane syndrome may explain some cases of infantile esotropia.

Methods: Three separate groups of patients were evaluated. 1) Families with features of infantile esotropia were identified through the Strabismus Inheritance Study Tasmania (SIST).

Analysis of optineurin (OPTN) gene mutations in subjects with and without glaucoma: the Blue Mountains Eye Study.

Background: The optineurin (OPTN) gene has been reported to possess both causal as well as risk-associated alleles for open-angle glaucoma. However, these findings have so far only been reported in family and clinic based studies. The aim of this study was to investigate the spectrum of mutations and gene variants in OPTN that might be present in people with glaucoma from a population-based study, the Blue Mountains Eye Study (BMES).

Arabidopsis RIN4 negatively regulates disease resistance mediated by RPS2 and RPM1 downstream or independent of the NDR1 signal modulator and is not required for the virulence functions of bacterial type III effectors AvrRpt2 or AvrRpm1.

Bacterial pathogens deliver type III effector proteins into the plant cell during infection. On susceptible (r) hosts, type III effectors can contribute to virulence. Some trigger the action of specific disease resistance (R) gene products.