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Nanophthalmos patient with a THR518MET mutation in MYRF, a case report
BACKGROUND: Nanophthalmos has a significant genetic background and disease-causing mutations have been recently been reported in the myelin regulatory factor (MYRF) gene. We report clinical features in a patient with nanophthalmos and a Thr518Met MYRF mutation. CASE PRESENTATION: A three-year-old ma...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528587/ https://www.ncbi.nlm.nih.gov/pubmed/33004036 http://dx.doi.org/10.1186/s12886-020-01659-8 |
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author | Hagedorn, Joshua Avdic, Armin Schnieders, Michael J. Roos, Benjamin R. Kwon, Young H. Drack, Arlene V. Boese, Erin A. Fingert, John H. |
author_facet | Hagedorn, Joshua Avdic, Armin Schnieders, Michael J. Roos, Benjamin R. Kwon, Young H. Drack, Arlene V. Boese, Erin A. Fingert, John H. |
author_sort | Hagedorn, Joshua |
collection | PubMed |
description | BACKGROUND: Nanophthalmos has a significant genetic background and disease-causing mutations have been recently been reported in the myelin regulatory factor (MYRF) gene. We report clinical features in a patient with nanophthalmos and a Thr518Met MYRF mutation. CASE PRESENTATION: A three-year-old male was discovered to have nanophthalmos after first presenting to the emergency department for a frontal headache, eye pain, emesis, and lethargy. Imaging studies (CT and MRI) were negative except for increased posterior fossa cerebrospinal fluid. Subsequent examinations revealed nanophthalmos (short axial eye lengths 18.1 mm OD and 18.3 mm OS), microcornea, and a large crystalline lens. Peripheral chorioretinal pigment abnormalities were also observed. He experienced episodes of marked ocular hypertension (53 mmHg OD and 60 mmHg) likely due to intermittent angle closure precipitated by nanophthalmos. The ocular hypertension was responsive to topical medicines. Genetic analysis of known nanophthalmos genes MFRP and TMEM98 were negative, while a novel mutation, Thr518Met was detected in MYRF. The Thr518Met mutation was absent from 362 matched normal controls and was extremely rare in a large population database, allele frequency of 0.000024. The Thr518Met mutation altered a highly conserved amino acid in the MYRF protein and three of four algorithms suggested that this mutation is likely pathogenic. Finally, molecular modeling showed that the Thr518Met mutation is damaging to MYRF structure. Together these data suggest that the Thr518Met mutation causes nanophthalmos. CONCLUSIONS: Nanophthalmos may present at an early age with features of angle closure glaucoma and a Thr518Met mutation in MYRF was detected in a patient with nanophthalmos. Prevalence data, homology data, mutation analysis data, and protein modeling data suggest that this variant is pathogenic and may expand the phenotypic range of syndromic nanophthalmos caused by MYRF mutations to include central nervous system abnormalities (increased posterior fossa cerebrospinal fluid). |
format | Online Article Text |
id | pubmed-7528587 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75285872020-10-02 Nanophthalmos patient with a THR518MET mutation in MYRF, a case report Hagedorn, Joshua Avdic, Armin Schnieders, Michael J. Roos, Benjamin R. Kwon, Young H. Drack, Arlene V. Boese, Erin A. Fingert, John H. BMC Ophthalmol Case Report BACKGROUND: Nanophthalmos has a significant genetic background and disease-causing mutations have been recently been reported in the myelin regulatory factor (MYRF) gene. We report clinical features in a patient with nanophthalmos and a Thr518Met MYRF mutation. CASE PRESENTATION: A three-year-old male was discovered to have nanophthalmos after first presenting to the emergency department for a frontal headache, eye pain, emesis, and lethargy. Imaging studies (CT and MRI) were negative except for increased posterior fossa cerebrospinal fluid. Subsequent examinations revealed nanophthalmos (short axial eye lengths 18.1 mm OD and 18.3 mm OS), microcornea, and a large crystalline lens. Peripheral chorioretinal pigment abnormalities were also observed. He experienced episodes of marked ocular hypertension (53 mmHg OD and 60 mmHg) likely due to intermittent angle closure precipitated by nanophthalmos. The ocular hypertension was responsive to topical medicines. Genetic analysis of known nanophthalmos genes MFRP and TMEM98 were negative, while a novel mutation, Thr518Met was detected in MYRF. The Thr518Met mutation was absent from 362 matched normal controls and was extremely rare in a large population database, allele frequency of 0.000024. The Thr518Met mutation altered a highly conserved amino acid in the MYRF protein and three of four algorithms suggested that this mutation is likely pathogenic. Finally, molecular modeling showed that the Thr518Met mutation is damaging to MYRF structure. Together these data suggest that the Thr518Met mutation causes nanophthalmos. CONCLUSIONS: Nanophthalmos may present at an early age with features of angle closure glaucoma and a Thr518Met mutation in MYRF was detected in a patient with nanophthalmos. Prevalence data, homology data, mutation analysis data, and protein modeling data suggest that this variant is pathogenic and may expand the phenotypic range of syndromic nanophthalmos caused by MYRF mutations to include central nervous system abnormalities (increased posterior fossa cerebrospinal fluid). BioMed Central 2020-10-01 /pmc/articles/PMC7528587/ /pubmed/33004036 http://dx.doi.org/10.1186/s12886-020-01659-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Case Report Hagedorn, Joshua Avdic, Armin Schnieders, Michael J. Roos, Benjamin R. Kwon, Young H. Drack, Arlene V. Boese, Erin A. Fingert, John H. Nanophthalmos patient with a THR518MET mutation in MYRF, a case report |
title | Nanophthalmos patient with a THR518MET mutation in MYRF, a case report |
title_full | Nanophthalmos patient with a THR518MET mutation in MYRF, a case report |
title_fullStr | Nanophthalmos patient with a THR518MET mutation in MYRF, a case report |
title_full_unstemmed | Nanophthalmos patient with a THR518MET mutation in MYRF, a case report |
title_short | Nanophthalmos patient with a THR518MET mutation in MYRF, a case report |
title_sort | nanophthalmos patient with a thr518met mutation in myrf, a case report |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528587/ https://www.ncbi.nlm.nih.gov/pubmed/33004036 http://dx.doi.org/10.1186/s12886-020-01659-8 |
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