Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma

Shimizu, Satoko; Lichter, Paul R.; Johnson, A. Tim; Zhou, Zhaohui; Higashi, Misao; Gottfreðsdóttir, María Soffía; Othman, Mohammad; Moroi, Sayoko E.; Rozsa, Frank W.; Schertzer, Robert M.; Clarke, Margo S.; Schwartz, Arthur L.; Downs, J. Crawford; Vollrath, Douglas; Richards, Julia E.

doi:10.1016/s0002-9394(00)00536-5

Cited by 145 publications

(138 citation statements)

References 43 publications

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“…Myocilin mutations are relatively common in patients with JOAG, and have been detected in 8-36% of patients in published case series. [30][31][32] The likelihood of detecting myocilin mutations in subjects with JOAG appears to be greater in patients with stronger family histories of glaucoma than in patients with apparently sporadic glaucoma. This table highlights the differences between mutations that primarily 'cause disease' on their own (such as the GLN368STOP mutation) and those that contribute to the overall risk for developing disease (such as the chromosome 7q31 risk allele).…”

Section: Myocilin (Myoc Omim #601652)mentioning

confidence: 99%

Primary open-angle glaucoma genes

Fingert

2011

Eye

193

175

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A substantial fraction of glaucoma has a genetic basis. About 5% of primary open angle glaucoma (POAG) is currently attributed to single-gene or Mendelian forms of glaucoma (ie glaucoma caused by mutations in myocilin or optineurin). Mutations in these genes have a high likelihood of leading to glaucoma and are rarely seen in normal subjects. Other cases of POAG have a more complex genetic basis and are caused by the combined effects of many genetic and environmental risk factors, each of which do not act alone to cause glaucoma. These factors are more frequently detected in patients with POAG, but are also commonly observed in normal subjects. Additional genes that may be important in glaucoma pathogenesis have been investigated using quantitative traits approaches. Such studies have begun to identify genes that control the magnitude of important quantitative features of glaucoma that may also be important risk factors for POAG, such as central corneal thickness. Each of these different approaches to study glaucoma genetics is providing new insights into the pathogenesis of POAG.

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Section: Myocilin (Myoc Omim #601652)mentioning

confidence: 99%

Primary open-angle glaucoma genes

Fingert

2011

Eye

193

175

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“…MYOC variants are highly penetrant: Age-related penetrance is complete at 50 years old for MYOC variants associated with an early age of onset 9,10,14,15 and almost complete at 75 years old for the common p.Gln368Ter variant. 13 Therefore, these unaffected individuals are expected to develop glaucoma at some stage.…”

Section: Response To Treatmentmentioning

confidence: 99%

“…7,8 MYOC disease-causing variants have been identified in 2-4% of unselected POAG patients and in 8-36% of POAG patients diagnosed before 40 years of age. [9][10][11] The variants are inherited in an autosomal dominant fashion with high penetrance, and carriers usually demonstrate elevated intraocular pressure (IOP) with an earlier age of onset than POAG patients without MYOC variants. 10 There is an enrichment of MYOC variants in patients with advanced POAG, indicating a progression to a more severe disease, particularly without treatment.…”

Section: Introductionmentioning

confidence: 99%

“…13 Other disease-causing variants such as p.Pro370Leu or p.Gly367Arg are more severe and are associated with complete penetrance by 50 years of age. 9,10,14,15 The exact mechanism of MYOC variants leading to disease has not yet been fully elucidated. There is evidence to suggest that the abnormal gene protein products accumulate in the trabecular meshwork contributing to outflow obstruction and ultimately increasing IOP.…”

Section: Introductionmentioning

confidence: 99%

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Myocilin Predictive Genetic Testing for Primary Open-Angle Glaucoma Leads to Early Identification of At-Risk Individuals

et al. 2017

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“…7,8 The most common mutation, Gln368X, has a mean age at diagnosis in the early 50s, 8,9 whereas other mutations, such as Pro370Leu, can be associated with an age at diagnosis as early as the teens. 10,11 Detecting a mutation in an unaffected individual does not predict the age of onset, the severity, or the progression of the condition but puts the person at a very high risk of developing glaucoma in his/her lifetime.…”

confidence: 99%

Predictive genetic testing experience for myocilin primary open-angle glaucoma using the Australian and New Zealand Registry of Advanced Glaucoma

Souzeau

Glading

Keane

et al. 2014

Genetics in Medicine

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Purpose: Predictive genetic testing of relatives of known myocilin (MYOC) gene mutation carriers is an appropriate strategy to identify individuals at risk for glaucoma. It is likely to prevent irreversible blindness in this high-risk group because this treatable condition might otherwise be diagnosed late. The Australian and New Zealand Registry of Advanced Glaucoma has established genetic testing protocols for known glaucoma genes, including MYOC. Methods:Through the Australian and New Zealand Registry of Advanced Glaucoma, we investigated the experience of 40 unaffected individuals who had undergone predictive genetic testing for MYOC mutations through questionnaires. Results:The main motivations for being tested were (i) to make appropriate interventions and (ii) to reduce uncertainty. All our respondents perceived strong benefits, either medical or emotional, in being tested. However, different concerns were raised by the respondents that need to be addressed during counseling. Greater family awareness was reported by the majority of the respondents, and the ability to provide information to children was a strong motivation for being tested. Conclusion:This study provides valuable information on the personal and familial impacts of having predictive genetic testing for glaucoma, which will help health professionals to better address the issues faced by patients and provide them adequate support.

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Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma

Cited by 145 publications

References 43 publications

Primary open-angle glaucoma genes

Primary open-angle glaucoma genes

Myocilin Predictive Genetic Testing for Primary Open-Angle Glaucoma Leads to Early Identification of At-Risk Individuals

Predictive genetic testing experience for myocilin primary open-angle glaucoma using the Australian and New Zealand Registry of Advanced Glaucoma

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