Retinal-specific guanylate cyclase gene mutations in Leber's congenital amaurosis

被引:365
作者
Perrault, I
Rozet, JM
Calvas, P
Gerber, S
Camuzat, A
Dollfus, H
Chatelin, S
Souied, E
Ghazi, I
Leowski, C
Bonnemaison, M
LePaslier, D
Frezal, J
Dufier, JL
Pittler, S
Munnich, A
Kaplan, J
机构
[1] HOP NECKER ENFANTS MALAD,UNITE RECH HANDICAPS GENET ENFANT,INSERM U393,F-75743 PARIS 15,FRANCE
[2] HOP NECKER ENFANTS MALAD,SERV OPHTALMOL,PARIS,FRANCE
[3] INST NATL JEUNES AVEUGLES,PARIS,FRANCE
[4] CTR ETUD POLYMORPHISME HUMAIN,F-75010 PARIS,FRANCE
[5] DEPT BIOCHEM & MOL BIOL,MOBILE,AL
[6] DEPT OPHTHALMOL,MOBILE,AL
关键词
D O I
10.1038/ng1296-461
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Leber's congenital amaurosis (LCA, MIM 204000(1)), the earliest and most severe form of inherited retinopathy, accounts for at least 5% of all inherited retinal dystrophies(2,3). This autosomal recessive condition is usually recognized at birth or during the first months of life in an infant with total blindness or greatly impaired vision, normal fundus and extinguished electroretinogram (ERG(4)). Nystagmus (pendular type) and characteristic eye poking are frequently observed in the first months of life (digito-ocular sign of Franceschetti(5)). Hypermetropia and keratoconus frequently develop in the course of the disease(6,7). The observation by Waardenburg(8) of nor mal children born to affected parents supports the genetic heterogeneity of LCA. Until now, however, little was known about the pathophysiology of the disease, but LCA is usually regarded as the consequence of either impaired development of photoreceptors or extremely early degeneration of cells that have developed normally(9). We have recently mapped a gene for LCA to chromosome 1.7p13.1 (LCA1) by homozygosity mapping in consanguineous families of North African origin and provided evidence of genetic heterogeneity in our sample, as LCA I accounted for 8/15 LCA families in our series(10,11). Here, we report two missense mutations (F589S) and two frameshift mutations (nt 460 del C, nt 693 del C) of the retinal guanylate cyclase (RETGC, GDB symbol GUC2D) gene in four unrelated LCA1 probands of North African ancestry and ascribe LCA1 to an impaired production of cGMP in the retina, with permanent closure of cGMP-gated cation channels.
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页码:461 / 464
页数:4
相关论文
共 30 条
[1]   CHROMOSOME MAPPING OF THE HUMAN ARRESTIN (SAG), BETA-ARRESTIN-2 (ARRB2), AND BETA-ADRENERGIC-RECEPTOR KINASE-2 (ADRBK2) GENES [J].
CALABRESE, G ;
SALLESE, M ;
STORNAIUOLO, A ;
STUPPIA, L ;
PALKA, G ;
DEBLASI, A .
GENOMICS, 1994, 23 (01) :286-288
[2]  
Camuzat A, 1996, HUM GENET, V97, P798
[3]   A GENE FOR LEBERS CONGENITAL AMAUROSIS MAPS TO CHROMOSOME 17P [J].
CAMUZAT, A ;
DOLLFUS, H ;
ROZET, JM ;
GERBER, S ;
BONNEAU, D ;
BONNEMAISON, M ;
BRIARD, ML ;
DUFIER, JL ;
GHAZI, I ;
LEOWSKI, C ;
WEISSENBACH, J ;
FREZAL, J ;
MUNNICH, A ;
KAPLAN, J .
HUMAN MOLECULAR GENETICS, 1995, 4 (08) :1447-1452
[4]   MOLECULAR MECHANISM OF VISUAL TRANSDUCTION [J].
CHABRE, M ;
DETERRE, P .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1989, 179 (02) :255-266
[5]   THE HUMAN PHOTORECEPTOR MEMBRANE GUANYLYL CYCLASE, RETGC, IS PRESENT IN OUTER SEGMENTS AND IS REGULATED BY CALCIUM AND A SOLUBLE ACTIVATOR [J].
DIZHOOR, AM ;
LOWE, DG ;
OLSHEVSKAYA, EV ;
LAURA, RP ;
HURLEY, JB .
NEURON, 1994, 12 (06) :1345-1352
[6]   MUTATIONS IN THE GENE ENCODING THE ALPHA-SUBUNIT OF THE ROD CGMP-GATED CHANNEL IN AUTOSOMAL RECESSIVE RETINITIS-PIGMENTOSA [J].
DRYJA, TP ;
FINN, JT ;
PENG, YW ;
MCGEE, TL ;
BERSON, EL ;
YAU, KW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (22) :10177-10181
[7]   LOCALIZATION OF THE GENE ENCODING HUMAN PHOSPHATIDYLINOSITOL TRANSFER PROTEIN (PITPN) TO 17P13.3 - A GENE SHOWING HOMOLOGY TO THE DROSOPHILA RETINAL DEGENERATION B-GENE (RDGB) [J].
FITZGIBBON, J ;
PILZ, A ;
GAYTHER, S ;
APPUKUTTAN, B ;
DULAI, KS ;
DELHANTY, JDA ;
HELMKAMP, GM ;
YARBROUGH, LR ;
HUNT, DM .
CYTOGENETICS AND CELL GENETICS, 1994, 67 (03) :205-207
[8]  
FOXMAN SG, 1985, ARCH OPHTHALMOL-CHIC, V103, P1502
[9]  
FRANCESCHETTI A, 1958, Ophthalmologica, V135, P610
[10]  
FRANCESCHETTI A, 1954, Confin Neurol, V14, P184