Mutations in the CEP290 (NPHP6) gene are a frequent cause of leber congenital amaurosis

被引：522

作者：

den Hollander, Anneke I.

Koenekoop, Robert K.

Yzer, Suzanne

Lopez, Irma

Arends, Maarten L.

Voesenek, Krysta E. J.

Zonneveld, Marijke N.

Strom, Tim M.

Meitinger, Thomas

Brunner, Han G.

Hoyng, Carel B.

van den Born, L. Ingeborgh

Rohrschneider, Klaus

Cremers, Frans P. M.

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands

[4] McGill Univ, Ctr Hlth, McGill Ocular Genet Ctr, Montreal, PQ, Canada

[5] Rotterdam Eye Hosp, Rotterdam, Netherlands

[6] Natl Res Ctr Environm & Hlth, German Sci Fdn, Inst Human Genet, Munich, Germany

[7] Heidelberg Univ, Dept Ophthalmol, Heidelberg, Germany

[8] Tech Univ Munich, Inst Human Genet, D-8000 Munich, Germany

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2006年 / 79卷 / 03期

关键词：

D O I：

10.1086/507318

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Leber congenital amaurosis (LCA) is one of the main causes of childhood blindness. To date, mutations in eight genes have been described, which together account for similar to 45% of LCA cases. We localized the genetic defect in a consanguineous LCA-affected family from Quebec and identified a splice defect in a gene encoding a centrosomal protein (CEP290). The defect is caused by an intronic mutation ( c. 2991+ 1655A -> G) that creates a strong splice-donor site and inserts a cryptic exon in the CEP290 messenger RNA. This mutation was detected in 16 (21%) of 76 unrelated patients with LCA, either homozygously or in combination with a second deleterious mutation on the other allele. CEP290 mutations therefore represent one of the most frequent causes of LCA identified so far.

引用

页码：556 / 561

页数：6

共 18 条

[1] Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and Leber congenital amaurosis [J].

Bowne, SJ ;

Sullivan, LS ;

Mortimer, SE ;

Hedstrom, L ;

Zhu, JY ;

Spellicy, CJ ;

Gire, AI ;

Hughbanks-Wheaton, D ;

Birch, DG ;

Lewis, RA ;

Heckenlively, JR ;

Daiger, SP .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (01) :34-42

[2] In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse [J].

Chang, Bo ;

Khanna, Hemant ;

Hawes, Norman ;

Jimeno, David ;

He, Shirley ;

Lillo, Concepcion ;

Parapuram, Sunil K. ;

Cheng, Hong ;

Scott, Alison ;

Hurd, Ron E. ;

Sayer, John A. ;

Otto, Edgar A. ;

Attanasio, Massimo ;

O'Toole, John F. ;

Jin, Genglin ;

Shou, Chengchao ;

Hildebrandt, Friedhelm ;

Williams, David S. ;

Heckenlively, John R. ;

Swaroop, Anand .

HUMAN MOLECULAR GENETICS, 2006, 15 (11) :1847-1857

[3] Molecular genetics of Leber congenital amaurosis [J].

Cremers, FPM ;

van den Hurk, JAJM ;

den Hollander, AI .

HUMAN MOLECULAR GENETICS, 2002, 11 (10) :1169-1176

[4] Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR [J].

Cremers, FPM ;

van De Pol, DJR ;

van Driel, M ;

den Hollander, AI ;

van Haren, FJJ ;

Knoers, NVAM ;

Tijmes, N ;

Bergen, AAB ;

Rohrschneider, K ;

Blankenagel, A ;

Pinckers, AJLG ;

Deutman, AF ;

Hoyng, CB .

HUMAN MOLECULAR GENETICS, 1998, 7 (03) :355-362

[5]

Dharmaraj S R, 2000, Ophthalmic Genet, V21, P135

[6] Predictive identification of exonic splicing enhancers in human genes [J].

Fairbrother, WG ;

Yeh, RF ;

Sharp, PA ;

Burge, CB .

SCIENCE, 2002, 297 (5583) :1007-1013

[7] Allegro, a new computer program for multipoint linkage analysis [J].

Gudbjartsson, DF ;

Jonasson, K ;

Frigge, ML ;

Kong, A .

NATURE GENETICS, 2000, 25 (01) :12-13

[8] Leber congenital amaurosis: Comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis [J].

Hanein, S ;

Perrault, I ;

Gerber, S ;

Tanguy, G ;

Barbet, F ;

Ducroq, D ;

Calvas, P ;

Dollfus, H ;

Hamel, C ;

Lopponen, T ;

Munier, F ;

Santos, L ;

Shalev, S ;

Zafeiriou, D ;

Dufier, JL ;

Munnich, A ;

Rozet, JM ;

Kaplan, J .

HUMAN MUTATION, 2004, 23 (04) :306-317

[9] easyLINKAGE-Plus - automated linkage analyses using large-scale SNP data [J].

Hoffmann, K ;

Lindner, TH .

BIOINFORMATICS, 2005, 21 (17) :3565-3567

[10] Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset severe retinal dystrophy [J].

Janecke, AR ;

Thompson, DA ;

Utermann, G ;

Becker, C ;

Hübner, CA ;

Schmid, E ;

McHenry, CL ;

Nair, AR ;

Rüschendorf, F ;

Heckenlively, J ;

Wissinger, B ;

Nurnberg, P ;

Gal, A .

NATURE GENETICS, 2004, 36 (08) :850-854

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