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Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients
We genetically characterized 22 Swiss patients who had been diagnosed with Stargardt disease after clinical examination. We identified in 11 patients (50%) pathogenic bi-allelic ABCA4 variants, c.1760+2T>C and c.4496T>C being novel. The dominantly inherited pathogenic ELOVL4 c.810C>G p.(Tyr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229718/ https://www.ncbi.nlm.nih.gov/pubmed/34073554 http://dx.doi.org/10.3390/genes12060812 |
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author | Buhler, Virginie M.M. Berger, Lieselotte Schaller, André Zinkernagel, Martin S. Wolf, Sebastian Escher, Pascal |
author_facet | Buhler, Virginie M.M. Berger, Lieselotte Schaller, André Zinkernagel, Martin S. Wolf, Sebastian Escher, Pascal |
author_sort | Buhler, Virginie M.M. |
collection | PubMed |
description | We genetically characterized 22 Swiss patients who had been diagnosed with Stargardt disease after clinical examination. We identified in 11 patients (50%) pathogenic bi-allelic ABCA4 variants, c.1760+2T>C and c.4496T>C being novel. The dominantly inherited pathogenic ELOVL4 c.810C>G p.(Tyr270*) and PRPH2-c.422A>G p.(Tyr141Cys) variants were identified in eight (36%) and three patients (14%), respectively. All patients harboring the ELOVL4 c.810C>G p.(Tyr270*) variant originated from the same small Swiss area, identifying a founder mutation. In the ABCA4 and ELOVL4 cohorts, the clinical phenotypes of “flecks”, “atrophy”, and “bull’s eye like” were observed by fundus examination. In the small number of patients harboring the pathogenic PRPH2 variant, we could observe both “flecks” and “atrophy” clinical phenotypes. The onset of disease, progression of visual acuity and clinical symptoms, inheritance patterns, fundus autofluorescence, and optical coherence tomography did not allow discrimination between the genetically heterogeneous Stargardt patients. The genetic heterogeneity observed in the relatively small Swiss population should prompt systematic genetic testing of clinically diagnosed Stargardt patients. The resulting molecular diagnostic is required to prevent potentially harmful vitamin A supplementation, to provide genetic counseling with respect to inheritance, and to schedule appropriate follow-up visits in the presence of increased risk of choroidal neovascularization. |
format | Online Article Text |
id | pubmed-8229718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82297182021-06-26 Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients Buhler, Virginie M.M. Berger, Lieselotte Schaller, André Zinkernagel, Martin S. Wolf, Sebastian Escher, Pascal Genes (Basel) Article We genetically characterized 22 Swiss patients who had been diagnosed with Stargardt disease after clinical examination. We identified in 11 patients (50%) pathogenic bi-allelic ABCA4 variants, c.1760+2T>C and c.4496T>C being novel. The dominantly inherited pathogenic ELOVL4 c.810C>G p.(Tyr270*) and PRPH2-c.422A>G p.(Tyr141Cys) variants were identified in eight (36%) and three patients (14%), respectively. All patients harboring the ELOVL4 c.810C>G p.(Tyr270*) variant originated from the same small Swiss area, identifying a founder mutation. In the ABCA4 and ELOVL4 cohorts, the clinical phenotypes of “flecks”, “atrophy”, and “bull’s eye like” were observed by fundus examination. In the small number of patients harboring the pathogenic PRPH2 variant, we could observe both “flecks” and “atrophy” clinical phenotypes. The onset of disease, progression of visual acuity and clinical symptoms, inheritance patterns, fundus autofluorescence, and optical coherence tomography did not allow discrimination between the genetically heterogeneous Stargardt patients. The genetic heterogeneity observed in the relatively small Swiss population should prompt systematic genetic testing of clinically diagnosed Stargardt patients. The resulting molecular diagnostic is required to prevent potentially harmful vitamin A supplementation, to provide genetic counseling with respect to inheritance, and to schedule appropriate follow-up visits in the presence of increased risk of choroidal neovascularization. MDPI 2021-05-26 /pmc/articles/PMC8229718/ /pubmed/34073554 http://dx.doi.org/10.3390/genes12060812 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Buhler, Virginie M.M. Berger, Lieselotte Schaller, André Zinkernagel, Martin S. Wolf, Sebastian Escher, Pascal Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients |
title | Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients |
title_full | Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients |
title_fullStr | Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients |
title_full_unstemmed | Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients |
title_short | Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients |
title_sort | absence of genotype/phenotype correlations requires molecular diagnostic to ascertain stargardt and stargardt-like swiss patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229718/ https://www.ncbi.nlm.nih.gov/pubmed/34073554 http://dx.doi.org/10.3390/genes12060812 |
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