Myocilinallele-specific glaucoma phenotype database

Abstract

Communicated by Daniel F. SchorderetGlaucoma, a complex heterogenous disease, is the leading cause for optic nerve-related blindness worldwide.Since 1997, when mutations in the myocilin (MYOC) gene were identified as causing juvenile onset as well as a proportion of primary open-angle glaucoma (POAG), more than 180 variants have been documented. Approximately one in 30 unselected patients with POAG have a disease-causing myocilin mutation and it has been shown that firm genotype-phenotype correlations exist. We have compiled an online catalog of myocilin variants and their associated phenotypes. This locus-specific resource, to which future submissions can be made, is available online (www.myocilin.com; last accessed 28 August 2007). The database, constructed using MySQL, contains three related sheets that contain data pertaining to the information source, variant identified, and relevant study data, respectively. The website contains a list of all identified variants and summary statistics as well as background genomic information, such as the annotated sequence and cross-protein/species homology. Phenotypic data such as the mean7standard deviation (SD) age at POAG diagnosis, mean7SD maximum recorded intraocular pressure, proportion of patients requiring surgical intervention, and age-related penetrance can be viewed by selecting a particular mutation. Approximately 40% of the identified sequence variants have been characterized as disease causing, with the majority (85%) of these being missense mutations. Preliminary data generated from this online resource highlight the strong genotype-phenotype correlations associated with specific myocilin mutations. The large-scale assimilation of relevant data allows for accurate comprehensive genetic counseling and the translation of genomic information into the clinic. Hum Mutat 29(2), [207][208][209][210][211] 2008.

Mortality in primary open-angle glaucoma: ‘two cupped discs and a funeral’

“…17,18 Interestingly the Myocilin gene, which has been unequivocally implicated in glaucoma and is not known to serve any physiological function, has been found to be highly expressed in the heart. 19,20 Using a clinic-based population, Tattersall et al 21 found that despite better IOP control, patients with OAG with a poor life expectancy lost more functional vision than severity-matched patients. In our study no association between disease severity and mortality cause was identified.…”

Molecular complexity of primary open angle glaucoma: current concepts

“…Mutations in myocilin largely have their effect by dominant negative gain of function mechanism (Lam et al 2000). A total of 66 point mutations are listed in the HGMD database (www.hgmd.cf.ac.uk/ac/index.php) but a more comprehensive overview is provided in the myocilin mutation database (www.myocilin.com) (Hewitt et al 2008), where till date 74 disease causing mutations are listed. Myocilin mutations are generally associated with juvenile or early-adult form of POAG.…”

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

“…[10][11][12] In order to reduce the variability accounted for by disease-causing variants of different severity, we analysed individuals carrying only the most common MYOC variant (p.Gln368Ter) separately.…”

“…10 Since the discovery of the MYOC gene in 1997, over 80 disease-causing variants have been described, with the p.Gln368Ter variant the most common. 12 Although clear genotype-phenotype correlations exist, inter-and intrafamilial phenotypic variability is also well acknowledged. The p.Gln368Ter variant has a variable age-related penetrance with 50% of carriers diagnosed with glaucoma by 50 years of age.…”