Journal article
Prevalence of MYOC mutations in a cohort of juvenile open-angle glaucoma (JOAG) patients from Sub-Saharan Africa
Ophthalmology. Glaucoma, Vol.8(5), pp.450-456
09/2025
DOI: 10.1016/j.ogla.2025.04.010
PMCID: PMC12459295
PMID: 40280414
Abstract
Determine the prevalence and the role of myocilin (MYOC) gene mutations in a sub-Saharan population of juvenile open-angle glaucoma (JOAG) patients
Prospective case-control
45 JOAG patients and 41 normal control subjects from the ophthalmology clinics of the University College Hospital Ibadan, Nigeria.
DNA was tested for MYOC coding sequence mutations using Sanger sequencing. Identified mutations were evaluated for pathogenicity by 1) ClinGen scoring 2) assessing prevalence in large public databases of patients with African ancestry (gnomAD and 1000 Genomes); and 3) Mutation analysis algorithms (PolyPhen, SIFT, Blosum62, MutationTaster, CADD, and AlphaMissense). The prevalence of variants was compared between JOAG patients and normal controls from Ibadan using a mutation burden analysis using SKAT-O.
Sanger DNA sequencing data indicating the presence or absence of glaucoma-causing mutations in the MYOC gene.
A total of 10 instances of 4 MYOC variants were detected. A p.Pro370Leu variant, which has been previously categorized by the ClinGen as Pathogenic, was detected in three (6.7%) of 45 JOAG probands. A p.Arg470Cys MYOC variant, previously categorized a Variant of Unknown Significance, was identified in one (2.2%) of 45 JOAG probands. A p.Glu352Lys variant, previously categorized as Benign, was detected in 2 (4.4%) of JOAG probands. Both the p.Pro370Leu and p.Arg470Cys variants were absent from control subjects and large public databases, while p.Glu352Lys was present at a frequency >1%, which is inconsistent with pathogenicity. Finally, synonymous missense variant, p.Glu396Glu, was also detected. Five of six mutation analysis algorithms supported the pathogenicity of the p.Pro370Leu and p.Arg470Cys variants, while slightly fewer (4 of 6) suggested that p.Glu352Lys is pathogenic.
MYOC mutations are the most common known cause of JOAG in populations of European ancestry. Our case-control study estimated the prevalence of pathogenic MYOC mutations to be 8.9% in an African population from Nigeria. MYOC mutations are the most common known cause of JOAG in sub-Saharan Africa, however, they account for a minority of cases.
Details
- Title: Subtitle
- Prevalence of MYOC mutations in a cohort of juvenile open-angle glaucoma (JOAG) patients from Sub-Saharan Africa
- Creators
- Olusola Olawoye - University of IbadanBrian P. Young - Carver College of Medicine, University of Iowa, Iowa City, IAAngela W. Nyunt - University of IowaOluwatoyin F. Fafowora - University of IbadanMagdalene AjaniBrendan A. Creemer - Interdisciplinary Program in Genetics, University of Iowa, Iowa City, Iowa, USABen R. Roos - Institute for Vision Research, University of Iowa, Iowa City, Iowa, USAAnne L. Coleman - Jules Stein Eye Institute, Los Angeles, CA, USAMichael B. Gorin - Jules Stein Eye Institute, Los Angeles, CA, USAMichael A. Hauser - Duke UniversityTodd E. Scheetz - Institute for Vision Research, University of Iowa, Iowa City, Iowa, USAAdeyinka Ashaye - University of IbadanJohn H. Fingert - Institute for Vision Research, University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Ophthalmology. Glaucoma, Vol.8(5), pp.450-456
- DOI
- 10.1016/j.ogla.2025.04.010
- PMID
- 40280414
- PMCID
- PMC12459295
- NLM abbreviation
- Ophthalmol Glaucoma
- ISSN
- 2589-4196
- eISSN
- 2589-4196
- Publisher
- Elsevier Inc
- Grant note
- National Institutes of Health: R01 EY035266
Funding for the work was provided in part by a Shaffer Grant from the Glaucoma Research Foundation (O.O.) ; Fogarty International Clinical Research Scholars and Fellows Program (O.F.) ; Unrestricted grants from Research to Prevent Blindness to the Departments of Ophthalmology at the University of Iowa and at UCLA; Grant for the Eyes of Africa: The genetics of blindness study; the UCLA Stein Eye Center for Community Outreach and Policy, The Hadley-Carver Chair in Glaucoma (J.H.F.) , The Donald Heineking Research Fund (J.H.F.) , the Harold and Pauline Price Chair (M.B.G.) , and the National Institutes of Health (R01 EY035266) . The sponsors or funding organizations had no role in the design or conduct of this research.r (M.B.G.) , and the National Institutes of Health (R01 EY035266) . The sponsors or funding organizations had no role in the design or conduct of this research.
- Language
- English
- Electronic publication date
- 04/23/2025
- Date published
- 09/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; The University of Iowa Institute for Vision Research; Ophthalmology and Visual Sciences
- Record Identifier
- 9984815911502771
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