Original articleGenetic Screening for OPA1 and OPA3 Mutations in Patients with Suspected Inherited Optic Neuropathies
Section snippets
Optic Atrophy Cohort
The study cohort consisted of 188 patients with bilateral optic atrophy referred for molecular investigations to the Emory Genetics Laboratory, a tertiary diagnostic facility with College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) accreditations. All affected individuals had been assessed by experienced neuro-ophthalmologists (VB, NRM, NJN) over a 6-year period from January 1, 2004, through December 31, 2009. A comprehensive examination was performed
OPA1 Mutations Identified
Using the PCR-based sequencing methods, 21 different OPA1 mutations were identified in 27 (14.4%) of the 188 probands screened: (1) missense (8/21; 38.1%), (2) deletion (7/21; 33.3%), (3) nonsense (4/21; 19.0%), (4) duplication (1/21; 4.8%), and (5) splice site mutations (1/21; 4.8%; Table 1, available at http://aaojournal.org). The mutational yield rate was significantly higher among individuals with a positive family history of visual failure (19/38; 50.0%) compared with presumed singleton
Discussion
OPA1 comprises 30 coding exons spread over 100 Kb of genomic DNA. It is a highly polymorphic gene with more than 200 pathogenic variants known to cause disease.18, 19 This study further extended the mutational spectrum of OPA1 and identified 6 novel mutations in families with nonsyndromic optic atrophy. The first OPA1 initiation codon mutation, c.1A→T was also identified, which is a rare molecular occurrence, but has been reported in other inherited ocular disorders.20, 21, 22, 23
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Heterozygous type 1 Autosomal Dominant Optic Atrophy (ADOA) with OPA1 c.1936-2A>G genetic variant
2020, Journal Francais d'OphtalmologieMeta-analysis of genotype-phenotype analysis of OPA1 mutations in autosomal dominant optic atrophy
2019, MitochondrionCitation Excerpt :A total of 408 individuals with ADOA were identified in the published reports. Patient information was obtained from the following sources: 47 were obtained from Yu-Wai-Man et al. (2010a,b), 45 from Yu-Wai-Man et al. (2010a,b), 38 from Cécile Delettre et al. (2000), 27 from Fuhrmann et al. (2009), 25 from Pesch et al. (2001), 22 from Nakamura et al. (2006); Puomila et al. (2005) respectively, 21 from Baris et al. (2003), 15 from Delettre et al. (2001), 14 from Payne et al. (2004), 10 from Almind et al. (2011), 9 each from Chen et al. (2000); Yen et al. (2010), 8 from Amati-Bonneau et al. (2008), 7 each from Alexander et al. (2000); Hudson et al. (2008); Schimpf et al. (2006); Stewart et al. (2008), 6 each from Cardaioli et al. (2006); Han et al. (2006), 5 each from Hamahata et al. (2012); Li et al. (2005); Shimizu et al. (2003); Spinazzi et al. (2008), 4 each from Amati-Bonneau et al. (2005); Puomila et al. (2005); Yamada (2003), 3 each from Pretegiani et al. (2011); Shimizu et al. (2002); Yu-Wai-Man et al., 2016a,b), 2 each from Hayashi, Gekka, Omoto, Takeuchi, & Kitahara (2005); Huang, Santarelli, & Starr (2009); Liguori et al. (2008), and one each from Amati-Bonneau & Pasquier (2003); Ban, Yoshida, Kawasaki, & Mochida (2007); Magnin, Allibert, Berger, Dollfus, & Rumbach (2012); Mizutari et al. (2010); Ranieri et al. (2012); Yu-Wai-Man et al. (2011). Patients were grouped into two categories: classic ADOA (with symptoms relating only to vision) and ADOA ‘plus’ (presence of extra-ocular manifestations); 71% of patients had classic ADOA (n = 288), and 29% had ADOA ‘plus’ (n = 120) (Table 1).
Idebenone Treatment in Patients with OPA1-Dominant Optic Atrophy: A Prospective Phase 2 Trial
2023, Neuro-OphthalmologyInherited optic neuropathies
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Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Supported in part by the National Institutes of Health, Bethesda, Maryland (core grant nos.: P30 EY 06360 and NIH R01 EY11916 [Department of Ophthalmology]; and an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York. Dr Yu-Wai-Man is an Medical Research Council (MRC, UK) Clinical Research Fellow in Neuro-Ophthalmology, and Dr Newman is the recipient of a Research to Prevent Blindness Lew R. Wasserman Merit Award.
Manuscript no. 2010-587.