Investigation of Founder Effects for the Thr377Met Myocilin Mutation in Glaucoma Families from Differing Ethnic Backgrounds

Purpose: The aim of this study was to determine if there is a common founder for the Thr377Met myocilin mutation in primary open angle glaucoma (POAG) families with various ethnic backgrounds. Methods: Genomic DNA of 24 POAG-affected individuals from nine pedigrees with the Thr377Met mutation and 104 unaffected family members was genotyped with six microsatellite markers and four single nucleotide polymorphisms. The families were from Greece, India, Finland, the USA, and Australia. To assess the degree of linkage disequilibrium across MYOC in the general population we also investigated data generated from the HapMap consortium. Results: Three distinct haplotypes associated with the Thr377Met myocilin mutation were identified. The families from the USA and Greece, as well as the three Australian families originating from Greece and the former Yugoslavian Republic of Macedonia had one common haplotype. Interestingly, however, HapMap data suggest that linkage disequilibrium across MYOC was not strong. Conclusions: The Thr377Met myocilin mutation has arisen at least three separate times. Evidence for genetic founder effects in this prevalent age-related, yet heterogeneous, disease has important implications for future gene identification strategies

Evaluation of the agreement and reliability of Transpalpebral Tonometers compared with Goldmann Applanation Tonometer – A systematic Review and Meta-Analysis Protocol

In 2020, the global prevalence of glaucoma was estimated to be 76 million and it was projected to increase to 111.8 million by 2040. Accurate intraocular pressure (IOP) measurement is imperative in glaucoma management since it is the only modifiable risk factor. Numerous studies have compared the reliability of IOP measured using transpalpebral tonometers and Goldmann applanation tonometry (GAT). This systematic review and meta-analysis aims to update the existing literature with a reliability and agreement comparison of transpalpebral tonometers against the gold standard GAT for IOP measurement among individuals presenting for ophthalmic examinations. The data collection will be performed using a predefined search strategy through electronic databases. Prospective methods-comparison studies published between January 2000 and September 2022 will be included. Studies will be deemed eligible if they report empirical findings on the agreement between transpalpebral tonometry and Goldmann applanation tonometry. The standard deviation and limits of agreement between each study and their pooled estimate along with weights and percentage of error will be reported using a forest plot. Cochrane's Q test and the I2 statistic will be used to assess heterogeneity, and the publication bias will be investigated using a funnel plot, Begg's and Egger's tests. The review results will provide additional evidence on the reliability of transpalpebral tonometers that, in turn, could possibly assist practitioners to make informed decision about using it as a screening or diagnostic device for clinical practice, outreach camps, or home-based screening. Institutional Ethics Committee registration number: RET202200390. PROSPERO Registration Number: CRD42022321693

PAX6 gene variations associated with aniridia in south India

<p>Abstract</p> <p>Background</p> <p>Mutations in the transcription factor gene <it>PAX6 </it>have been shown to be the cause of the aniridia phenotype. The purpose of this study was to analyze patients with aniridia to uncover <it>PAX6 </it>gene mutations in south Indian population.</p> <p>Methods</p> <p>Total genomic DNA was isolated from peripheral blood of twenty-eight members of six clinically diagnosed aniridia families and 60 normal healthy controls. The coding exons of the human <it>PAX6 </it>gene were amplified by PCR and allele specific variations were detected by single strand conformation polymorphism (SSCP) followed by automated sequencing.</p> <p>Results</p> <p>The sequencing results revealed novel <it>PAX6 </it>mutations in three patients with sporadic aniridia: c.715ins5, [c.1201delA; c.1239A>G] and c.901delA. Two previously reported nonsense mutations were also found: c.482C>A, c.830G>A. A neutral polymorphism was detected (IVS9-12C>T) at the boundary of intron 9 and exon 10. The two nonsense mutations found in the coding region of human <it>PAX6 </it>gene are reported for the first time in the south Indian population.</p> <p>Conclusion</p> <p>The genetic analysis confirms that haploinsuffiency of the <it>PAX6 </it>gene causes the classic aniridia phenotype. Most of the point mutations detected in our study results in stop codons. Here we add three novel <it>PAX6 </it>gene mutations in south Indian population to the existing spectrum of mutations, which is not a well-studied ethnic group. Our study supports the hypothesis that a mutation in the <it>PAX6 </it>gene correlates with expression of aniridia.</p