Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Buhler, Virginie M.M., Berger, Lieselotte, Schaller, André, Zinkernagel, Martin S., Wolf, Sebastian, Escher, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783713043745603584
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
work_keys_str_mv AT buhlervirginiemm absenceofgenotypephenotypecorrelationsrequiresmoleculardiagnostictoascertainstargardtandstargardtlikeswisspatients
AT bergerlieselotte absenceofgenotypephenotypecorrelationsrequiresmoleculardiagnostictoascertainstargardtandstargardtlikeswisspatients
AT schallerandre absenceofgenotypephenotypecorrelationsrequiresmoleculardiagnostictoascertainstargardtandstargardtlikeswisspatients
AT zinkernagelmartins absenceofgenotypephenotypecorrelationsrequiresmoleculardiagnostictoascertainstargardtandstargardtlikeswisspatients
AT wolfsebastian absenceofgenotypephenotypecorrelationsrequiresmoleculardiagnostictoascertainstargardtandstargardtlikeswisspatients
AT escherpascal absenceofgenotypephenotypecorrelationsrequiresmoleculardiagnostictoascertainstargardtandstargardtlikeswisspatients