Genomics combined with a protein informatics platform to assess a novel pathogenic variant c.1024 A>G (p.K342E) in OPA1 in a patient with autosomal dominant optic atrophy.

BACKGROUND: Autosomal Dominant Optic Atrophy (ADOA) is caused by mutations in the Optic Atrophy 1 Gene which disrupts the OPA1 protein. This disruption affects the normal function of the protein; impairs fusion of the mitochondrial inner membrane; and prevents normal OPA1 protein degradation. These events cause damage in retinal ganglion cells that could affect the patients with symptoms ranging from none to legally blind. MATERIALS AND METHODS: Our study identifies a missense variant mutation, c.1024 A > G (p.K342E), in OPA1 gene causing ADOA. Diagnosed clinically in three family members and the presence of this mutation was confirmed in two members by genetic testing. Pathogenic variants in OPA1 impact the secondary protein structure and function by causing non-conservative amino acid substitutions. We also modeled this mutation and compared it to the wild type using statistical mechanics. RESULTS AND CONCLUSIONS: The proband's pathogenic variant, c.1024 A > G (p.K342E), is located in the GTPase domain of OPA1 and causes changes in the protein structure by affecting the oligomerization pattern thus resulting in ADOA. Identifying the pathogenic potential of the missense mutations in the OPA1 gene using neoteric protein modeling techniques would help in the early detection of ADOA in patients who have family history of blindness. This action would help in providing early follow up, possible treatment in the future, and genetic counseling. Abbreviations: ADOA: Autosomal Dominant Optic Atrophy; CYCS: Caspase Activator Cytochrome C; OPA1: Optic Atrophy Gene 1; RGC: Retinal Ganglion Cells; VUS: Variant of Uncertain Significance.

Intraocular lens power calculations in eyes with previous hyperopic laser in situ keratomileusis or photorefractive keratectomy.

PURPOSE: To evaluate the accuracy of 7 intraocular lens (IOL) calculation formulas in patients with previous hyperopic laser in situ keratomileusis (LASIK) or excimer laser photorefractive keratectomy (PRK). DESIGN: Retrospective case series. SETTING: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, and private practice, Mesa, Arizona, USA. METHODS: The 7 formulas evaluated were the adjusted Atlas 0-3, Masket, Modified Masket, Haigis-L, Shammas-PL, Barrett True-K, and Barrett True-K No-History. The Masket and Modified Masket were calculated using the single-K version of Holladay 1 and Hoffer Q formulas; the adjusted Atlas 0-3 was calculated using the double-K version of Holladay 1 and Hoffer Q. The IOL power predicted by each formula was calculated by targeting the postoperative manifest refraction. The IOL prediction error was obtained by subtracting the predicted IOL power from the implanted IOL power. The mean IOL prediction error, median absolute refractive prediction error, and percentages of eyes within ±0.50 diopter (D) and ±1.00 D of the predicted refraction were calculated. RESULTS: Twenty-one eyes of 21 patients were evaluated. There were no significant differences in the median absolute refractive prediction error or percentages of eyes within ±0.50 D or ±1.00 D of the predicted refraction between formulas or methods. The IOL mean prediction errors were comparable between the Holladay 1 and Hoffer Q calculations for all formulas except for a greater error for the double-K version of the Hoffer Q of the adjusted Atlas 0-3. CONCLUSION: In eyes that had hyperopic LASIK or PRK, there were no significant differences in the accuracy between the 7 IOL calculation formulas.