Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration

Science

Volumn 277, Issue 5333, 1997, Pages 1805-1807

  Allikmets, Rando ^a   Shroyer, Noah F ^b   Singh, Nanda ^c   Seddon, Johanna M ^d   Lewis, Richard Alan ^b   Bernstein, Paul S ^c   Peiffer, Andy ^c   Zabriskie, Norman A ^c   Li, Yixin ^b   Hutchinson, Amy ^e   Dean, Michael ^e   Lupski, James R ^b   Leppert, Mark ^c  

^a SAIC FREDERICK INC   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGING; ARTICLE; GENE DELETION; GENE MUTATION; HUMAN; LASER COAGULATION; PHOTORECEPTOR; PIGMENT EPITHELIUM; PRIORITY JOURNAL; RETINA MACULA AGE RELATED DEGENERATION; RETINA MACULA DEGENERATION; RETINA ROD; VISUAL IMPAIRMENT;

ADULT; AGED; AGED, 80 AND OVER; ATP-BINDING CASSETTE TRANSPORTERS; FEMALE; FRAMESHIFT MUTATION; HETEROZYGOTE; HUMANS; MACULA LUTEA; MACULAR DEGENERATION; MALE; MIDDLE AGED; MUTATION; PEDIGREE; PIGMENT EPITHELIUM OF EYE; RETINAL DRUSEN; SEQUENCE DELETION;

EID: 0012119330     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.277.5333.1805     Document Type: Article

References (31)

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19. Patients were selected from ophthalmic clinic populations (the Massachusetts Eye and Ear Infirmary, Boston, MA; and the Moran Eye Center-University of Utah, Salt Lake City, UT). AMD was defined as ophthalmoscopically identifiable macular pathology, including macular drusen, RPE detachment, geographic atrophy, exudative AMD including RPE detachment, choroidal neovascularizatjon, or disciform scar (18). Individuals were excluded if they had other causes of disciform or exudative maculopathy similar to AMD, such as ocular histoplasmosis syndrome, myopic chorioretinal degeneration without or with lacquer cracks, pseudoxanthoma elasticum and other associations of angioid streaks, basal laminar drusen, or post-traumatic choroidal ruptures. Also excluded were individuals with any other retinal and retinal vascular pathology (retinitis pigmentosa, vascular occlusive disease, or diabetic retinopathy). The retinal photographs and fluorescein angiograms of every patient with an ABCR alteration were reviewed in a masked fashion with those of matched individuals without alterations to confirm assignment of affected status and to ensure exclusion of Stargardt disease. STGD1 patients were evaluated as in (13). Controls were U.S. Caucasians from the general population collected for other studies. Among the 167 patients, 59 (36%) were male and 108 (64%) were female; one was African-American and the remainder were European-American. Of the 26 individuals with AMD-associated alterations, 25% were male and 75% were female.
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22. -7). Considering only alterations also found in STGD1 patients (G863A, R1898H, G1961E, and 6519del11) (23) and D2177N yields 16/167 in AMD patients and 3/220 in controls. A total of 21 AMD patients but only 1 control had nonconservative ABCR alterations (charge alterations, splice site variants, or frame shifts). The aggregate frequency of all variants was 35% in AMD patients and 31% in controls. Whether the more common ABCR variants affect function remains to be determined.
23. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; R, Arg; S, Ser; and T, Thr.
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31. We thank the participating patients, their families, and their physicians for cooperation; A. Crandall, M. Swartz, and M. Teske at the Moran Eye Center; M. Sullivan and C. Tucker at the Massachusetts Eye and Ear Infirmary; S. Cevario and R. Workman for technical assistance; G. Huttley for statistical advice; and the University of Utah Health Sciences Sequencing Facility. Supported by grants from the Foundation Fighting Blindness (R.A.L. and J.R.L.), Research to Prevent Blindness (R.A.L., J.M.S., P.S.B., and N.A.Z.), the Steinbach Fund (J.R.L. and R.A.L.), the W. M. Keck Foundation (M.L. and A.P.), the Macular Degeneration Foundation of Boston (J.M.S.), the Tornquist Charitable Foundation (M.L.), and the National Eye Institute (J.R.L., R.A.L., J.M.S., and N.F.S.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.