Monoallelic ABCA4 mutations appear insufficient to cause retinopathy: A quantitative autofluorescence study

Investigative Ophthalmology and Visual Science

Volumn 56, Issue 13, 2015, Pages 8179-8186

  Müller, Philipp L ^a,b   Gliem, Martin ^a,b   Mangold, Elisabeth ^a   Bolz, Hanno J ^c,d   Finger, Robert P ^a,e   McGuinness, Myra ^e   Betz, Christian ^c   Jiang, Zhichun ^f   Weber, Bernhard H F ^g   Maclaren, Robert E ^h   Holz, Frank G ^a,b   Radu, Roxana A ^f   Issa, Peter Charbel ^a,b  

^a UNIVERSITY OF BONN   (Germany)

^b UNIVERSITY HOSPITAL BONN   (Germany)

^c Bioscientia Center for Human Genetics   (Germany)

^d UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^e UNIVERSITY OF MELBOURNE   (Australia)

^f JULES STEIN EYE INSTITUTE   (United States)

^g UNIVERSITY OF REGENSBURG   (Germany)

^h UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Abca4; Carrier; Monoallelic; Phenotype; Quantitative fundus autofluorescence

Indexed keywords

ABC TRANSPORTER; GENOMIC DNA; LIPOFUSCIN; RETINOID DERIVATIVE; ABCA4 PROTEIN, HUMAN; DNA;

ADULT; ARTICLE; AUTOFLUORESCENCE; BIOCHEMICAL ANALYSIS; BLOOD ANALYSIS; CLINICAL ARTICLE; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; EYE FUNDUS; FEMALE; GENETIC SCREENING; GENOTYPE; HUMAN; IMAGE ANALYSIS; MALE; MIDDLE AGED; MISSENSE MUTATION; MOUSE; MULTIPLEX LIGATION DEPENDENT PROBE AMPLIFICATION; MUTATION; NEXT GENERATION SEQUENCING; NONHUMAN; PHENOTYPE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; RETINOPATHY; ALLELE; ANIMAL; DISEASE MODEL; DNA MUTATIONAL ANALYSIS; FLUORESCENCE ANGIOGRAPHY; GENETICS; KNOCKOUT MOUSE; METABOLISM; OPTICAL COHERENCE TOMOGRAPHY; PATHOLOGY; RETINA DISEASE; RETINAL PIGMENT EPITHELIUM; RETROSPECTIVE STUDY;

ADULT; ALLELES; ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; CROSS-SECTIONAL STUDIES; DISEASE MODELS, ANIMAL; DNA; DNA MUTATIONAL ANALYSIS; FEMALE; FLUORESCEIN ANGIOGRAPHY; FUNDUS OCULI; HUMANS; MALE; MICE; MICE, KNOCKOUT; MIDDLE AGED; MUTATION; PHENOTYPE; RETINAL DISEASES; RETINAL PIGMENT EPITHELIUM; RETROSPECTIVE STUDIES; TOMOGRAPHY, OPTICAL COHERENCE;

EID: 84952941794     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.15-17629     Document Type: Article

References (42)

1. Allikmets R, Singh N, Sun H, et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet. 1997;15: 236-246.
2. Cremers FP, van de Pol DJ, van Driel M, et al. Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt’s disease gene ABCR. Hum Mol Genet. 1998;7:355-362.
3. Maugeri A, Klevering BJ, Rohrschneider K, et al. Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy. Am J Hum Genet. 2000;67:960-966.
4. Klevering BJ, Deutman AF, Maugeri A, Cremers FP, Hoyng CB. The spectrum of retinal phenotypes caused by mutations in the ABCA4 gene. Graefes Arch Clin Exp Ophthalmol. 2005; 243:90-100.
5. Michaelides M, Chen LL, Brantley MA Jr, et al. ABCA4 mutations and discordant ABCA4 alleles in patients and siblings with bull’s-eye maculopathy. Br J Ophthalmol. 2007; 91:1650-1655.
6. Delori FC, Staurenghi G, Arend O, Dorey CK, Goger DG, Weiter JJ. In vivo measurement of lipofuscin in Stargardt’s disease-fundus flavimaculatus. Invest Ophthalmol Vis Sci. 1995;36:2327-2331.
7. Cideciyan AV, Aleman TS, Swider M, et al. Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence. Hum Mol Genet. 2004;13:525-534.
8. Burke TR, Duncker T, Woods RL, et al. Quantitative fundus autofluorescence in recessive Stargardt disease. Invest Ophthalmol Vis Sci. 2014;55:2841-2852.
9. Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci. 1995;36:718-729.
10. Eagle RC Jr, Lucier AC, Bernardino VB Jr, Yanoff M. Retinal pigment epithelial abnormalities in fundus flavimaculatus: a light and electron microscopic study. Ophthalmology. 1980; 87:1189-1200.
11. Birnbach CD, Jarvelainen M, Possin DE, Milam AH. Histopathology and immunocytochemistry of the neurosensory retina in fundus flavimaculatus. Ophthalmology. 1994;101:1211-1219.
12. Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice. Cell. 1999;98:13-23.
13. Charbel Issa P, Barnard AR, Singh MS, et al. Fundus autofluorescence in the Abca4/ mouse model of Stargardt disease-correlation with accumulation of A2E, retinal function and histology. Invest Ophthalmol Vis Sci. 2013;54:5602-5612.
14. Allikmets R, Shroyer NF, Singh N, et al. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science. 1997;277:1805-1807.
15. Allikmets R. Further evidence for an association of ABCR alleles with age-related macular degeneration. The International ABCR Screening Consortium. Am J Hum Genet. 2000; 67:487-491.
16. Souied EH, Ducroq D, Gerber S, et al. Age-related macular degeneration in grandparents of patients with Stargardt disease: genetic study. Am J Ophthalmol. 1999;128:173-178.
17. Stone EM, Webster AR, Vandenburgh K, et al. Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration. Nat Genet. 1998;20:328-329.
18. Guymer RH, Heon E, Lotery AJ, et al. Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration. Arch Ophthalmol. 2001; 119:745-751.
19. De La Paz MA, Guy VK, Abou-Donia S, et al. Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration. Ophthalmology. 1999;106:1531-1536.
20. Fritsche LG, Fleckenstein M, Fiebig BS, et al. A subgroup of age-related macular degeneration is associated with mono-allelic sequence variants in the ABCA4 gene. Invest Ophthal- mol Vis Sci. 2012;53:2112-2118.
21. Westeneng-van Haaften SC, Boon CJ, Cremers FP, Hoefsloot LH, den Hollander AI, Hoyng CB. Clinical and genetic characteristics of late-onset Stargardt’s disease. Ophthalmology. 2012;119:1199-1210.
22. Delori F, Greenberg JP, Fischer J, et al. Quantitative measurements of autofluorescence with the scanning laser ophthal-moscope. Invest Ophthalmol Vis Sci. 2011;52:9379-9390.
23. Eisenberger T, Neuhaus C, Khan AO, et al. Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies. PLoS One. 2013;8:e78496.
24. Schwarz JM, Rödelsperger C, Schuelke M, Seelow D. MutationTaster evaluates disease-causing potential of sequence alterations. Nat Methods. 2010;7:575-576.
25. Ng PC, Henikoff S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31:3812-3814.
26. Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013;Chapter 7:Unit7.20.
27. Helb HM, Charbel Issa P, Fleckenstein M, et al. Clinical evaluation of simultaneous confocal scanning laser ophthal-moscopy imaging combined with high-resolution spectral-domain optical coherence tomoggraphy. Acta Ophthalmol. 2010;88:842-849.
28. van de Kraats J, van Norren D. Optical density of the aging human ocular media in the visible and the UV. J Opt Soc Am A Opt Image Sci Vis. 2007;24:1842-1857.
29. Greenberg JP, Duncker T, Woods RL, Smith RT, Sparrow JR, Delori FC. Quantitative fundus autofluorescence in healthy eyes. Invest Ophthalmol Vis Sci. 2013;54:5684-5693.
30. Mattapallil MJ, Wawrousek EF, Chan CC, et al. The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci. 2012; 53:2921-2927.
31. Radu RA, Hu J, Yuan Q, et al. Complement system dysregulation and inflammation in the retinal pigment epithelium of a mouse model for Stargardt macular degeneration. J Biol Chem. 2011;286:18593-18601.
32. Parish CA, Hashimoto M, Nakanishi K, Dillon J, Sparrow J. Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium. Proc Natl Acad Sci U S A. 1998;95:14609-14613.
33. Rozet JM, Gerber S, Souied E, et al. Spectrum of ABCR gene mutations in autosomal recessive macular dystrophies. Eur J Hum Genet. 1998;6:291-295.
34. Shroyer NF, Lewis RA, Allikmets R, et al. The rod photoreceptor ATP-binding cassette transporter gene, ABCR, and retinal disease: from monogenic to multifactorial. Vision Res. 1999; 39:2537-2544.
35. Fujinami K, Zernant J, Chana RK, et al. Clinical and molecular characteristics of childhood-onset Stargardt disease. Ophthalmology. 2014;122:326-334.
36. Quazi F, Lenevich S, Molday RS. ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer. Nat Commun. 2012;3:925.
37. Ablonczy Z, Higbee D, Grey AC, Koutalos Y, Schey KL, Crouch RK. Similar molecules spatially correlate with lipofuscin and N-retinylidene-N-retinylethanolamine in the mouse but not in the human retinal pigment epithelium. Arch Biochem Biophys. 2013;539:196-202.
38. Mata NL, Tzekov RT, Liu X, Weng J, Birch DG, Travis GH. Delayed dark-adaptation and lipofuscin accumulation in abcrþ/mice: implications for involvement of ABCR in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2001;42:1685-1690.
39. Kim SR, Fishkin N, Kong J, Nakanishi K, Allikmets R, Sparrow JR. Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2E. Proc Natl Acad Sci U S A. 2004;101:11668-11672.
40. Mata NL, Weng J, Travis GH. Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc Natl Acad Sci USA. 2000;97: 7154-7159.
41. Auricchio A, Trapani I, Allikmets R. Gene therapy of ABCA4-associated diseases. Cold Spring Harb Perspect Med. 2015;5: a017301.
42. Charbel Issa P, De Silva SR, Lipinski DM, et al. Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina. PLoS One. 2013;8:e60361.