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Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation
PURPOSE: To describe the complex, overlapping phenotype expressed in a two generation family harboring pathogenic mutations in the ABCA4 and GPR143 genes. METHODS: Clinical evaluation of a two generation family included quantitative autofluorescence imaging (qAF, 488-nm excitation) using a modified...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961055/ https://www.ncbi.nlm.nih.gov/pubmed/27367509 http://dx.doi.org/10.1167/iovs.16-19621 |
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author | Lee, Winston Schuerch, Kaspar Xie, Yajing Zernant, Jana Tsang, Stephen H. Sparrow, Janet R. Allikmets, Rando |
author_facet | Lee, Winston Schuerch, Kaspar Xie, Yajing Zernant, Jana Tsang, Stephen H. Sparrow, Janet R. Allikmets, Rando |
author_sort | Lee, Winston |
collection | PubMed |
description | PURPOSE: To describe the complex, overlapping phenotype expressed in a two generation family harboring pathogenic mutations in the ABCA4 and GPR143 genes. METHODS: Clinical evaluation of a two generation family included quantitative autofluorescence imaging (qAF, 488-nm excitation) using a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for varying laser power detector sensitivity, spectral-domain optical coherence tomography, and full-field ERG testing. Complete sequencing of the ABCA4 and GPR143 genes was carried out in each individual. RESULTS: Affected individuals presented with bull's eye lesions and qAF levels above the 95% confidence interval for healthy eyes; full-field ERG revealed no generalized rod dysfunction but mild implicit time delays in cone responses. Complete sequencing of the ABCA4 gene revealed two disease-causing mutations, p.L541P and p.G1961E; and mutational phase was confirmed in each unaffected parent. Further examination in the affected patients revealed a peripheral “mud-splattered” pattern of hypopigmented RPE after which sequencing of GPR143 revealed a novel missense variant, p.Y157C. The GPR143 variant segregated from the father who did not exhibit any indications of retinal disease with the exception of an abnormal near-infrared autofluorescence (NIR-AF) signal distribution in the macula. CONCLUSIONS: An individual carrying both ABCA4 and GPR143 disease-causing mutations can express a complex, overlapping phenotype associated with both Stargardt disease and X-linked ocular albinism (OA1). The absence of OA1-related disease changes (with the exception of NIR-AF changes associated with melanin distribution) in the father may be indicative of mild expressivity or variable gene penetrance. |
format | Online Article Text |
id | pubmed-4961055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-49610552016-12-01 Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation Lee, Winston Schuerch, Kaspar Xie, Yajing Zernant, Jana Tsang, Stephen H. Sparrow, Janet R. Allikmets, Rando Invest Ophthalmol Vis Sci Genetics PURPOSE: To describe the complex, overlapping phenotype expressed in a two generation family harboring pathogenic mutations in the ABCA4 and GPR143 genes. METHODS: Clinical evaluation of a two generation family included quantitative autofluorescence imaging (qAF, 488-nm excitation) using a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for varying laser power detector sensitivity, spectral-domain optical coherence tomography, and full-field ERG testing. Complete sequencing of the ABCA4 and GPR143 genes was carried out in each individual. RESULTS: Affected individuals presented with bull's eye lesions and qAF levels above the 95% confidence interval for healthy eyes; full-field ERG revealed no generalized rod dysfunction but mild implicit time delays in cone responses. Complete sequencing of the ABCA4 gene revealed two disease-causing mutations, p.L541P and p.G1961E; and mutational phase was confirmed in each unaffected parent. Further examination in the affected patients revealed a peripheral “mud-splattered” pattern of hypopigmented RPE after which sequencing of GPR143 revealed a novel missense variant, p.Y157C. The GPR143 variant segregated from the father who did not exhibit any indications of retinal disease with the exception of an abnormal near-infrared autofluorescence (NIR-AF) signal distribution in the macula. CONCLUSIONS: An individual carrying both ABCA4 and GPR143 disease-causing mutations can express a complex, overlapping phenotype associated with both Stargardt disease and X-linked ocular albinism (OA1). The absence of OA1-related disease changes (with the exception of NIR-AF changes associated with melanin distribution) in the father may be indicative of mild expressivity or variable gene penetrance. The Association for Research in Vision and Ophthalmology 2016-06-28 2016-06 /pmc/articles/PMC4961055/ /pubmed/27367509 http://dx.doi.org/10.1167/iovs.16-19621 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Genetics Lee, Winston Schuerch, Kaspar Xie, Yajing Zernant, Jana Tsang, Stephen H. Sparrow, Janet R. Allikmets, Rando Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation |
title | Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation |
title_full | Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation |
title_fullStr | Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation |
title_full_unstemmed | Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation |
title_short | Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation |
title_sort | simultaneous expression of abca4 and gpr143 mutations: a complex phenotypic manifestation |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961055/ https://www.ncbi.nlm.nih.gov/pubmed/27367509 http://dx.doi.org/10.1167/iovs.16-19621 |
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