title: Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation.
abstract: To describe the complex, overlapping phenotype expressed in a two generation family harboring pathogenic mutations in the ABCA4 and GPR143 genes.
  
  
  
  Clinical evaluation of a two generation family included quantitative autofluorescence imaging (qAF, 488-nm excitation) using a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for varying laser power detector sensitivity, spectral-domain optical coherence tomography, and full-field ERG testing. Complete sequencing of the ABCA4 and GPR143 genes was carried out in each individual.
  
  
  
  Affected individuals presented with bull's eye lesions and qAF levels above the 95% confidence interval for healthy eyes; full-field ERG revealed no generalized rod dysfunction but mild implicit time delays in cone responses. Complete sequencing of the ABCA4 gene revealed two disease-causing mutations, p.L541P and p.G1961E; and mutational phase was confirmed in each unaffected parent. Further examination in the affected patients revealed a peripheral "mud-splattered" pattern of hypopigmented RPE after which sequencing of GPR143 revealed a novel missense variant, p.Y157C. The GPR143 variant segregated from the father who did not exhibit any indications of retinal disease with the exception of an abnormal near-infrared autofluorescence (NIR-AF) signal distribution in the macula.
  
  
  
  An individual carrying both ABCA4 and GPR143 disease-causing mutations can express a complex, overlapping phenotype associated with both Stargardt disease and X-linked ocular albinism (OA1). The absence of OA1-related disease changes (with the exception of NIR-AF changes associated with melanin distribution) in the father may be indicative of mild expressivity or variable gene penetrance.
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: Kaspar
authors.initials: K
authors.lastname: Schuerch
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Xie
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 2Department 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 2Department of Pathology & Cell Biology, Columbia University, New York, New York, United States.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States 2Department 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*; D000293:Adolescent; D000328:Adult; D016117:Albinism, Ocular / Q000235:genetics / Q000378:metabolism*; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018613:Microscopy, Confocal; D009154:Mutation; D010641:Phenotype; D012160:Retina / Q000473:pathology / Q000503:physiopathology; D017422:Sequence Analysis, DNA; D000080362:Stargardt Disease
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D005136:Eye Proteins; C095276:GPR143 protein, human; D008562:Membrane Glycoproteins