A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy

被引:1072
作者
Allikmets, R
Singh, N
Sun, H
Shroyer, NE
Hutchinson, A
Chidambaram, A
Gerrard, B
Baird, L
Stauffer, D
Peiffer, A
Rattner, A
Smallwood, P
Li, YX
Anderson, KL
Lewis, RA
Nathans, J
Leppert, M
Dean, M
Lupski, JR
机构
[1] NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, LAB GEN DIVERS, FREDERICK, MD 21702 USA
[2] NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, INTRAMURAL RES SUPPORT PROGRAM, FREDERICK, MD 21702 USA
[3] UNIV UTAH, DEPT HUMAN GENET, SALT LAKE CITY, UT 84112 USA
[4] JOHNS HOPKINS UNIV, SCH MED, DEPT MOL BIOL & GENET, BALTIMORE, MD 21205 USA
[5] JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA
[6] JOHNS HOPKINS UNIV, SCH MED, DEPT OPHTHALMOL, BALTIMORE, MD 21205 USA
[7] JOHNS HOPKINS UNIV, SCH MED, HOWARD HUGHES MED INST, BALTIMORE, MD 21205 USA
[8] BAYLOR COLL MED, DEPT MOL & HUMAN GENET, HOUSTON, TX 77030 USA
[9] BAYLOR COLL MED, DEPT PEDIAT, HOUSTON, TX 77030 USA
[10] BAYLOR COLL MED, DEPT OPHTHALMOL, HOUSTON, TX 77030 USA
[11] BAYLOR COLL MED, DEPT MED, HOUSTON, TX 77030 USA
关键词
D O I
10.1038/ng0397-236
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Stargardt disease (STGD, also known as fundus flavimaculatus; FFM) is an autosomal recessive retinal disorder characterized by a juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. A gene encoding an ATP-binding cassette (ABC) transporter was mapped to the 2-cM (centiMorgan) interval at 1p13-p21 previously shown by linkage analysis to harbour the STGD gene. This gene, ABCR, is expressed exclusively and at high levels in the retina, in rod but not cone photoreceptors, as detected by in situ hybridization. Mutational analysis of ABCR in STGD families revealed a total of 19 different mutations including homozygous mutations in two families with consanguineous parentage. These data indicate that ABCR is the causal gene of STGD/FFM.
引用
收藏
页码:236 / 246
页数:11
相关论文
共 78 条
[41]   The ATP binding cassette transporter ABC1, is required for the engulfment of corpses generated by apoptotic cell death [J].
Luciani, MF ;
Chimini, G .
EMBO JOURNAL, 1996, 15 (02) :226-235
[42]   CLONING OF 2 NOVEL ABC TRANSPORTERS MAPPING ON HUMAN-CHROMOSOME-9 [J].
LUCIANI, MF ;
DENIZOT, F ;
SAVARY, S ;
MATTEI, MG ;
CHIMINI, G .
GENOMICS, 1994, 21 (01) :150-159
[43]  
MCDONNELL PJ, 1986, OPHTHALMOLOGY, V93, P116
[44]   A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3) [J].
Meindl, A ;
Dry, K ;
Herrmann, K ;
Manson, F ;
Ciccodicola, A ;
Edgar, A ;
Carvalho, MRS ;
Achatz, H ;
Hellebrand, H ;
Lennon, A ;
Migliaccio, C ;
Porter, K ;
Zrenner, E ;
Bird, A ;
Jay, M ;
Lorenz, B ;
Wittwer, B ;
DUrso, M ;
Meitinger, T ;
Wright, A .
NATURE GENETICS, 1996, 13 (01) :35-42
[45]   NORRIE DISEASE IS CAUSED BY MUTATIONS IN AN EXTRACELLULAR PROTEIN RESEMBLING C-TERMINAL GLOBULAR DOMAIN OF MUCINS [J].
MEINDL, A ;
BERGER, W ;
MEITINGER, T ;
VANDEPOL, D ;
ACHATZ, H ;
DORNER, C ;
HAASEMANN, M ;
HELLEBRAND, H ;
GAL, A ;
CREMERS, F ;
ROPERS, HH .
NATURE GENETICS, 1992, 2 (02) :139-143
[46]   MOLECULAR MODELING OF THE NORRIE DISEASE PROTEIN PREDICTS A CYSTINE KNOT GROWTH-FACTOR TERTIARY STRUCTURE [J].
MEITINGER, T ;
MEINDL, A ;
BORK, P ;
ROST, B ;
SANDER, C ;
HAASEMANN, M ;
MURKEN, J .
NATURE GENETICS, 1993, 5 (04) :376-380
[47]  
MICHAELIS S, 1995, COLD SPRING HARBOR S, V60
[48]   PUTATIVE X-LINKED ADRENOLEUKODYSTROPHY GENE SHARES UNEXPECTED HOMOLOGY WITH ABC TRANSPORTERS [J].
MOSSER, J ;
DOUAR, AM ;
SARDE, CO ;
KIOSCHIS, P ;
FEIL, R ;
MOSER, H ;
POUSTKA, AM ;
MANDEL, JL ;
AUBOURG, P .
NATURE, 1993, 361 (6414) :726-730
[49]  
*NAT ADV EYE COUNC, 1993, NIH PUBLICATION
[50]   MOLECULAR-GENETICS OF HUMAN COLOR-VISION - THE GENES ENCODING BLUE, GREEN, AND RED PIGMENTS [J].
NATHANS, J ;
THOMAS, D ;
HOGNESS, DS .
SCIENCE, 1986, 232 (4747) :193-202