Cargando…
Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene
BACKGROUND: The purpose of this study was to identify the genetic cause and describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six unrelated probands. METHODS: We identified two white Czech, two white British and two South Asian families with a clinical diagnosis of SCD. Ophthalm...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142341/ https://www.ncbi.nlm.nih.gov/pubmed/30223810 http://dx.doi.org/10.1186/s12886-018-0918-8 |
_version_ | 1783355838449057792 |
---|---|
author | Evans, Cerys J. Dudakova, Lubica Skalicka, Pavlina Mahelkova, Gabriela Horinek, Ales Hardcastle, Alison J. Tuft, Stephen J. Liskova, Petra |
author_facet | Evans, Cerys J. Dudakova, Lubica Skalicka, Pavlina Mahelkova, Gabriela Horinek, Ales Hardcastle, Alison J. Tuft, Stephen J. Liskova, Petra |
author_sort | Evans, Cerys J. |
collection | PubMed |
description | BACKGROUND: The purpose of this study was to identify the genetic cause and describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six unrelated probands. METHODS: We identified two white Czech, two white British and two South Asian families with a clinical diagnosis of SCD. Ophthalmic assessment included spectral domain optical coherence tomography (SD-OCT) of one individual with advanced disease, and SD-OCT and confocal microscopy of a child with early stages of disease. UBIAD1 coding exons were amplified and Sanger sequenced in each proband. A fasting serum lipid profile was measured in three probands. Paternity testing was performed in one family. RESULTS: A novel heterozygous c.527G>A; p.(Gly176Glu) mutation in UBIAD1 was identified in one Czech proband. In the second Czech proband, aged 6 years when first examined, a previously described de novo heterozygous c.289G>A; p.(Ala97Thr) mutation was found. Two probands of South Asian descent carried a known c.305G>A; p.(Asn102Ser) mutation in the heterozygous state. Previously reported heterozygous c.361C>T; p.(Leu121Phe) and c.308C>T; p.(Thr103Ile) mutations were found in two white British families. Although crystalline deposits were present in all probands the affected area was small in some individuals. Corneal arcus and stromal haze were the most prominent phenotypical feature in two probands. In the Czech probands, SD-OCT confirmed accumulation of reflective material in the anterior stroma. Crystalline deposits were visualized by confocal microscopy. Mild dyslipidemia was found in all three individuals tested. CONCLUSION: Although de novo occurrence of mutations in UBIAD1 is extremely rare, SCD should be considered in the differential diagnosis of bilateral corneal haze and/or crystal deposition, especially in children. |
format | Online Article Text |
id | pubmed-6142341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61423412018-09-20 Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene Evans, Cerys J. Dudakova, Lubica Skalicka, Pavlina Mahelkova, Gabriela Horinek, Ales Hardcastle, Alison J. Tuft, Stephen J. Liskova, Petra BMC Ophthalmol Research Article BACKGROUND: The purpose of this study was to identify the genetic cause and describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six unrelated probands. METHODS: We identified two white Czech, two white British and two South Asian families with a clinical diagnosis of SCD. Ophthalmic assessment included spectral domain optical coherence tomography (SD-OCT) of one individual with advanced disease, and SD-OCT and confocal microscopy of a child with early stages of disease. UBIAD1 coding exons were amplified and Sanger sequenced in each proband. A fasting serum lipid profile was measured in three probands. Paternity testing was performed in one family. RESULTS: A novel heterozygous c.527G>A; p.(Gly176Glu) mutation in UBIAD1 was identified in one Czech proband. In the second Czech proband, aged 6 years when first examined, a previously described de novo heterozygous c.289G>A; p.(Ala97Thr) mutation was found. Two probands of South Asian descent carried a known c.305G>A; p.(Asn102Ser) mutation in the heterozygous state. Previously reported heterozygous c.361C>T; p.(Leu121Phe) and c.308C>T; p.(Thr103Ile) mutations were found in two white British families. Although crystalline deposits were present in all probands the affected area was small in some individuals. Corneal arcus and stromal haze were the most prominent phenotypical feature in two probands. In the Czech probands, SD-OCT confirmed accumulation of reflective material in the anterior stroma. Crystalline deposits were visualized by confocal microscopy. Mild dyslipidemia was found in all three individuals tested. CONCLUSION: Although de novo occurrence of mutations in UBIAD1 is extremely rare, SCD should be considered in the differential diagnosis of bilateral corneal haze and/or crystal deposition, especially in children. BioMed Central 2018-09-17 /pmc/articles/PMC6142341/ /pubmed/30223810 http://dx.doi.org/10.1186/s12886-018-0918-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. |
spellingShingle | Research Article Evans, Cerys J. Dudakova, Lubica Skalicka, Pavlina Mahelkova, Gabriela Horinek, Ales Hardcastle, Alison J. Tuft, Stephen J. Liskova, Petra Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene |
title | Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene |
title_full | Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene |
title_fullStr | Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene |
title_full_unstemmed | Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene |
title_short | Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene |
title_sort | schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the ubiad1 gene |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142341/ https://www.ncbi.nlm.nih.gov/pubmed/30223810 http://dx.doi.org/10.1186/s12886-018-0918-8 |
work_keys_str_mv | AT evanscerysj schnydercornealdystrophyandassociatedphenotypescausedbynovelandrecurrentmutationsintheubiad1gene AT dudakovalubica schnydercornealdystrophyandassociatedphenotypescausedbynovelandrecurrentmutationsintheubiad1gene AT skalickapavlina schnydercornealdystrophyandassociatedphenotypescausedbynovelandrecurrentmutationsintheubiad1gene AT mahelkovagabriela schnydercornealdystrophyandassociatedphenotypescausedbynovelandrecurrentmutationsintheubiad1gene AT horinekales schnydercornealdystrophyandassociatedphenotypescausedbynovelandrecurrentmutationsintheubiad1gene AT hardcastlealisonj schnydercornealdystrophyandassociatedphenotypescausedbynovelandrecurrentmutationsintheubiad1gene AT tuftstephenj schnydercornealdystrophyandassociatedphenotypescausedbynovelandrecurrentmutationsintheubiad1gene AT liskovapetra schnydercornealdystrophyandassociatedphenotypescausedbynovelandrecurrentmutationsintheubiad1gene |