The Molecular Genetic and Clinical Findings in two Probands with Stargardt Disease


Authors: B. Kousal 1,5;  J. Záhlava 2;  Š. Vejvalková 3;  M. Hejtmánková 4;  P. Lišková 1,5
Authors‘ workplace: Oãní klinika, 1. lékafiská fakulta, Univerzita Karlova v Praze a V‰eobecná fakultní nemocnice v Praze, pfiednostka doc. MUDr. Bohdana Kalvodová, CSc. 1;  Oãní klinika JL, s. r. o., primáfi MUDr. Ján Le‰ták, CSc., FEBO, MBA, LL. A FAOG 2;  Ústav biologie a lékafiské genetiky, 2. lékafiská fakulta, Univerzita Karlova v Praze a Fakultní nemocnice v Motole pfiednosta prof. MUDr. Milan Macek jr. DrSc. 3;  GENNET, Praha, vedoucí MUDr. David Stejskal 4;  Laboratofi biologie a patologie oka Ústav dûdiãn˘ch metabolick˘ch poruch 1. lékafiská fakulta, Univerzita Karlova v Praze a V‰eobecná fakultní nemocnice v Praze, pfiednosta prof. MUDr. Viktor KoÏich, CSc. 5
Published in: Čes. a slov. Oftal., 70, 2014, No. 6, p. 228-233
Category: Original Article

Overview

Purpose:
The aim of our study was to describe the phenotype and to perform molecular genetic investigation in two probands of Czech origin diagnosed with Stargardt disease (STGD).

Methods:
Both males underwent ocular examination including assessment by high-resolution spectral domain optical coherence tomography (SD-OCT). DNA was isolated from venous blood. Mutation detection was performed using the ABCA4 genotyping microarray (Asper Ophthalmics, Estonia).

Results:
The best corrected visual acuity in proband 1 (aged 39 years) was 0.1 bilaterally, and 0.05 in proband 2 (aged 26 years). Fundus examination showed typical multiple yellow-white lesions and macular atrophy. Alterations of retinal pigment epithelium, retinal thinning and disruption of the photoreceptor inner segment ellipsoid band were detected with an SD-OCT. Two known disease-causing mutations in ABCA4 were identified in proband 1; c.4234C>T, p.(Gln1412*) in exon 28; and c.5882G>A, p.(Gly1961Glu) in exon 42. Only one pathogenic change was detected in proband 2; c.1988G>A, p.(Trp663*) in exon 14. A second change, anticipated because of the recessive status of the disease, was not identified.

Conclusion:
The frequency and full spectrum of ABCA4 mutations in Czech patients with inherited retinal disorders is yet to be established. The inability to detect a second pathogenic change in ABCA4 coding sequences in proband 2 warrants further investigation.

Key words:
Stargardt disease, ABCA4, mutation, SD-OCT


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