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

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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)

Division/Institute:

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) > Clinics of Human Genetics

UniBE Contributor:

Bühler, Virginie Manuela Marie; Berger, Lieselotte Erika; Schaller, André; Zinkernagel, Martin Sebastian; Wolf, Sebastian and Escher, Pascal

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2073-4425

Publisher:

MDPI, Molecular Diversity Preservation International

Language:

English

Submitter:

Sebastian Wolf

Date Deposited:

07 Oct 2021 15:08

Last Modified:

07 Oct 2021 15:17

Publisher DOI:

10.3390/genes12060812

PubMed ID:

34073554

Uncontrolled Keywords:

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

BORIS DOI:

10.48350/159565

URI:

https://boris.unibe.ch/id/eprint/159565

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