Glaucoma phenotype in a large Swiss pedigree with the myocilin Gly367Arg mutation

Iliev, Milko E; Bodmer, S; Gallati, Sabina; Lanz, R; Stürmer, Jörg; Κatsoulis, Κonstantinos; Wolf, Sebastian; Trittibach, P.; Sarra, Gian-Marco

doi:10.1038/sj.eye.6702745

Cited by 14 publications

(10 citation statements)

References 24 publications

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“…Diagnosis JOAG (Cobb et al, 2002; Gupta et al, 2020; Iliev et al, 2008; Kanagavalli, Krishnadas, Pandaranayaka, Krishnaswamy, & Sundaresan, 2003; Souzeau et al, 2015; Vincent et al, 2002; Yao et al, 2018) POAG (J. Chen et al, 2011; Faucher et al, 2002; Mansergh et al, 1998; Melki, Belmouden, Brezin, & Garchon, 2003; K. G. Michels‐Rautenstrauss et al, 1998; Suzuki et al, 1997; Fumiko Taniguchi, Suzuki, Shirato, & Araie, 2000) …”

Section: Introductionmentioning

confidence: 99%

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Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data

et al. 2021

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Rare variants of the olfactomedin domain of myocilin are considered causative for inherited, early-onset open-angle glaucoma, with a misfolding toxic gain-of-function pathogenic mechanism detailed by 20 years of laboratory research. Myocilin variants are documented in the scientific literature and identified through large-scale genetic sequencing projects such as those curated in the Genome Aggregation Database (gnomAD). In the absence of key clinical and laboratory information, however, the pathogenicity of any given variant is not clear, because glaucoma is a heterogeneous and prevalent age-onset disease, and common variants are likely benign. In this review, we reevaluate the likelihood of pathogenicity for the~100 nonsynonymous missense, insertion-deletion, and premature termination of myocilin olfactomedin variants documented in the literature. We integrate available clinical, laboratory cellular, biochemical and biophysical data, the olfactomedin domain structure, and population genetics data from gnomAD. Of the variants inspected,~50% can be binned based on a preponderance of data, leaving many of uncertain pathogenicity that motivate additional studies. Ultimately, the approach of combining metrics from different disciplines will likely resolve outstanding complexities regarding the role of this misfolding-prone protein within the context of a multifactorial and prevalent ocular disease, and pave the way for new precision medicine therapeutics.

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Section: Introductionmentioning

confidence: 99%

“…JOAG (Cobb et al, 2002; Gupta et al, 2020; Iliev et al, 2008; Kanagavalli, Krishnadas, Pandaranayaka, Krishnaswamy, & Sundaresan, 2003; Souzeau et al, 2015; Vincent et al, 2002; Yao et al, 2018)…”

Section: Introductionmentioning

confidence: 99%

Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data

et al. 2021

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“…These families displayed two previously reported Myocilin mutations: p.T438I and p.G367R. Both variants have previously been reported in individuals displaying an age at diagnosis in childhood or early adulthood, significantly elevated IOP, and glaucoma surgery required for most individuals . Family A carrying p.T438I exhibited a similar phenotype.…”

Section: Discussionmentioning

confidence: 68%

Predictive genetic testing in minors for Myocilin juvenile onset open angle glaucoma

et al. 2015

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Myocilin glaucoma is an autosomal dominant disorder leading to irreversible blindness, but early intervention can minimize vision loss and delay disease progression. The purpose of this study was to discuss the benefits of predictive genetic testing in minors for Myocilin mutations associated with childhood onset glaucoma. Three families with Myocilin mutations associated with an age of onset before 18 years and six unaffected at‐risk children were identified. Predictive genetic testing was discussed with the parents and offered for at‐risk minors. Parents opted for genetic testing in half of the cases. None carried the familial mutation. The age of disease onset in the family, the severity of the condition, and the age of the child are all factors that appear to influence the decision of the parent to test their children. Predictive genetic testing for early onset Myocilin glaucoma can facilitate early detection of disease or discharge from routine ophthalmic examinations.

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“…[13] Mutations of MYOC have been reported associated with POAG pedigrees in many different ethnic groups. [1415161718192021] As a result, in this study, we first screened for the mutations in MYOC gene in a five-generation Chinese POAG pedigree. A heterozygous missense mutation, c.1456C<T (p.L486F), was found to locate at nucleotide 1456 in exon 3 of MYOC gene of all six affected and three unaffected members (IV: 11, V: 3, and V: 5).…”

Section: Discussionmentioning

confidence: 99%

Identification of Mutations in Myocilin and Beta-1,4-galactosyltransferase 3 Genes in a Chinese Family with Primary Open-angle Glaucoma

Liao

Zhong

et al. 2016

Chinese Medical Journal

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Background:Glaucoma is a major cause of irreversible blindness worldwide. There is evidence showing that a subset of the disease is genetically determined. In this study, we screened for mutations in chromosome 1q-linked open-angle glaucoma (GLC1A) in a Chinese family with primary open-angle glaucoma (POAG).Methods:A total of 23 members from five generations of a family were enrolled and underwent thorough ophthalmologic examinations. In addition, 200 unrelated healthy Chinese controls were also recruited as normal control. GLC1A gene was amplified by polymerase chain reaction, and DNA sequencing was performed to screen for mutations.Results:Six members were diagnosed as POAG, with severe clinical manifestations, and history of high intraocular pressures. The mean age of disease onset was 26.3 years. However, the others were asymptomatic. In six affected and three asymptomatic members, gene sequencing revealed a mutation c.C1456T in exon 3 of myocilin gene (MYOC). Furthermore, we also identified a novel mutation c.G322A in beta-1,4-galactosyltransferase 3 (B4GALT3) gene in all six affected and three asymptomatic members, which was not reported previously in POAG patients. The two newly identified variants were absent in other family members as well as controls.Conclusion:The mutations c.1456C

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Glaucoma phenotype in a large Swiss pedigree with the myocilin Gly367Arg mutation

Cited by 14 publications

References 24 publications

Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data

Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data

Predictive genetic testing in minors for Myocilin juvenile onset open angle glaucoma

Identification of Mutations in Myocilin and Beta-1,4-galactosyltransferase 3 Genes in a Chinese Family with Primary Open-angle Glaucoma

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