title: Structural and genetic assessment of the ABCA4-associated optical gap phenotype.
abstract: OBJECTIVE
  To investigate the developmental stages and genetic etiology of the optical gap phenotype in recessive Stargardt disease (STGD1).
  
  
  METHODS
  Single and longitudinal data points from 15 patients, including four sibling pairs, exhibiting an optical gap phenotype on spectral-domain optical coherence tomography (SD-OCT) with confirmed disease-causing ABCA4 alleles were retrospectively analyzed. Fundus images with corresponding SD-OCT scans were collected with a confocal scanning laser ophthalmoscope. Structural phenotypes were assigned to three developmental stages according to SD-OCT. The ABCA4 gene was screened in all patients.
  
  
  RESULTS
  At least two disease-causing ABCA4 variants where identified in each patient; all except one (91%) were compound heterozygous for the p.G1961E mutation. All patients exhibited structural findings on SD-OCT that grouped into three progressive developmental stages over several years. Stage 1 was characterized by mild disruptions of the ellipsoid zone (EZ) band over the fovea. Stage 2 was a progressive expansion of the EZ band loss resulting in an empty lesion devoid of photoreceptors. Stage 3 observed a structural collapse of the inner retinal layers into the optical gap space leading to involvement and atrophy of the RPE thereafter.
  
  
  CONCLUSIONS
  The optical gap phenotype in STGD1 can be structurally divided into three progressive stages spanning several years. This particular phenotype also appears to be highly associated with the p.G1961E mutation of ABCA4. Taken together, it appears that a focal loss of photoreceptors sequentially precedes RPE dysfunction in the early development of ABCA4-associated optical gap lesions.
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States Eye Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: Kalev
authors.initials: K
authors.lastname: Nõupuu
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Winston
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States Department of Pathology & Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States Department of Pathology & Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D010641:Phenotype; D012160:Retina / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012189:Retrospective Studies; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D004247:DNA
keywords: ABCA4; Stargardt disease; optical coherence tomography; optical gap; p.G1961E mutation