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 (2021). Absence of Genotype/Phenotype Correlations Requires Molecular Diagnostic to Ascertain Stargardt and Stargardt-Like Swiss Patients. Genes, 12(6) MDPI, Molecular Diversity Preservation International 10.3390/genes12060812

genes-12-00812-v3.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (9MB) | Preview

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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Human Genetics

UniBE Contributor:

Bühler, Virginie Manuela Marie, Berger, Lieselotte Erika, Schaller, André, Zinkernagel, Martin Sebastian, Wolf, Sebastian (B), Escher, Pascal


600 Technology > 610 Medicine & health




MDPI, Molecular Diversity Preservation International




Sebastian Wolf

Date Deposited:

07 Oct 2021 15:08

Last Modified:

05 Dec 2022 15:53

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Stargardt disease central areolar choroidal dystrophy choroidal dystrophy dominant inheritance genetic analyses macula dystrophy recessive inheritance retinal degeneration





Actions (login required)

Edit item Edit item
Provide Feedback