This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (83)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in this journal  Topic Collections  • Genetics  • Genetic Counseling/ Testing/ Therapy  • Alert me on articles by topic  Social Bookmarking   What's this?

Andrew J. Lotery, MD, FRCOphth; Samuel G. Jacobson, MD, PhD; Gerald A. Fishman, MD; Richard G. Weleber, MD; Anne B. Fulton, MD; P. Namperumalsamy, MD; Elise Héon, MD; Alex V. Levin, MD; Sandeep Grover, MD; Justin R. Rosenow, BS; Kelly K. Kopp, BS; Val C. Sheffield, MD, PhD; Edwin M. Stone, MD, PhD

Arch Ophthalmol. 2001;119:415-420.

Objectives  To test the hypothesis that mutations in the CRB1 gene cause Leber congenital amaurosis (LCA) and, if so, to describe the ocular phenotype of patients with LCA who harbor CRB1 sequence variations.

Patients  One hundred ninety probands with a clinical diagnosis of LCA were selected from a cohort of 233 probands ascertained in 5 different countries. The remaining 43 probands (18%) were excluded because they harbored sequence variations in previously identified LCA genes.

Methods  One hundred ninety unrelated individuals with LCA were screened for coding sequence mutations in the CRB1 gene with single-strand conformation polymorphism analysis followed by automated DNA sequencing.

Results  Twenty-one of the 190 probands (9% of the total cohort of 233) and 2 (1.4%) of 140 controls harbored amino acid–altering sequence variations in the CRB1 gene (P = .003).

Conclusions  In our cohort of patients with LCA, coding sequence variations were observed in the CRB1 gene more frequently than in any of the other 5 known LCA-associated genes. Likely disease-causing sequence variations have now been identified in 64 (28%) of 233 subjects in this cohort.

Clinical Relevance  Molecular diagnosis can confirm and clarify the diagnosis in an increasing fraction of patients with LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations may be established. This will facilitate the counseling of patients regarding their visual prognosis and the likelihood of associated systemic anomalies.

From the University of Iowa College of Medicine, Iowa City (Drs Lotery, Sheffield, and Stone, Mr Rosenow, and Ms Kopp); the Scheie Eye Institute, Philadelphia, Pa (Dr Jacobson); the University of Illinois Eye and Ear Infirmary, Chicago (Drs Fishman and Grover); the Casey Eye Institute, Portland, Ore (Dr Weleber); Children's Hospital, Boston, Mass (Dr Fulton); Aravind Eye Hospital, Madurai, India (Dr Namperumalsamy); the Eye Research Institute of Canada (Dr Héon), and The Hospital for Sick Children (Dr Levin), Toronto, Ontario.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED ARTICLES

Implications of Genetic Analysis in Leber Congenital Amaurosis
David M. Gamm and Andrew T. Thliveris
Arch Ophthalmol. 2001;119(3):426-427.
EXTRACT | FULL TEXT  

Archives of Ophthalmology Reader's Choice: Continuing Medical Education
Arch Ophthalmol. 2001;119(3):464.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

CRB1 Gene Mutations Are Associated with Keratoconus in Patients with Leber Congenital Amaurosis
McMahon et al.
IOVS 2009;50:3185-3187.
ABSTRACT | FULL TEXT  

Mutation Screening of 299 Spanish Families with Retinal Dystrophies by Leber Congenital Amaurosis Genotyping Microarray
Vallespin et al.
IOVS 2007;48:5653-5661.
ABSTRACT | FULL TEXT  

An Assessment of the Apex Microarray Technology in Genotyping Patients with Leber Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy
Henderson et al.
IOVS 2007;48:5684-5689.
ABSTRACT | FULL TEXT  

The N1317H Substitution Associated with Leber Congenital Amaurosis Results in Impaired Interdomain Packing in Human CRB1 Epidermal Growth Factor-like (EGF) Domains
Davis et al.
J. Biol. Chem. 2007;282:28807-28814.
ABSTRACT | FULL TEXT  

Clinical and Molecular Genetics of Leber's Congenital Amaurosis: A Multicenter Study of Italian Patients
Simonelli et al.
IOVS 2007;48:4284-4290.
ABSTRACT | FULL TEXT  

Unraveling the Genetic Complexity of Drosophila stardust During Photoreceptor Morphogenesis and Prevention of Light-Induced Degeneration
Berger et al.
Genetics 2007;176:2189-2200.
ABSTRACT | FULL TEXT  

The Phenotype of Early-Onset Retinal Degeneration in Persons with RDH12 Mutations
Schuster et al.
IOVS 2007;48:1824-1831.
ABSTRACT | FULL TEXT  

Genetic Testing for Inherited Eye Disease
Stone
Arch Ophthalmol 2007;125:205-212.
FULL TEXT  

Mosaic Eyes is a novel component of the Crumbs complex and negatively regulates photoreceptor apical size
Hsu et al.
Development 2006;133:4849-4859.
ABSTRACT | FULL TEXT  

Towards understanding CRUMBS function in retinal dystrophies
Richard et al.
Hum Mol Genet 2006;15:R235-R243.
ABSTRACT | FULL TEXT  

CRB1 Heterozygotes with Regional Retinal Dysfunction: Implications for Genetic Testing of Leber Congenital Amaurosis.
Yzer et al.
IOVS 2006;47:3736-3744.
ABSTRACT | FULL TEXT  

Microarray-based mutation detection and phenotypic characterization of patients with leber congenital amaurosis.
Yzer et al.
IOVS 2006;47:1167-1176.
ABSTRACT | FULL TEXT  

Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa
Booij et al.
J. Med. Genet. 2005;42:e67-e67.
ABSTRACT | FULL TEXT  

Identification of Novel Murine- and Human-Specific RPGRIP1 Splice Variants with Distinct Expression Profiles and Subcellular Localization
Lu and Ferreira
IOVS 2005;46:1882-1890.
ABSTRACT | FULL TEXT  

MPP5 Recruits MPP4 to the CRB1 Complex in Photoreceptors
Kantardzhieva et al.
IOVS 2005;46:2192-2201.
ABSTRACT | FULL TEXT  

Pigmented Paravenous Chorioretinal Atrophy Is Associated with a Mutation within the Crumbs Homolog 1 (CRB1) Gene
McKay et al.
IOVS 2005;46:322-328.
ABSTRACT | FULL TEXT  

Fundus Autofluorescence in Patients with Leber Congenital Amaurosis
Scholl et al.
IOVS 2004;45:2747-2752.
ABSTRACT | FULL TEXT  

The Phenotype of Leber Congenital Amaurosis in Patients With AIPL1 Mutations
Dharmaraj et al.
Arch Ophthalmol 2004;122:1029-1037.
ABSTRACT | FULL TEXT  

Cellular Localization of the MPP4 Protein in the Mammalian Retina
Stohr et al.
IOVS 2003;44:5067-5074.
ABSTRACT | FULL TEXT  

Distinct roles of Bazooka and Stardust in the specification of Drosophila photoreceptor membrane architecture
Hong et al.
Proc. Natl. Acad. Sci. USA 2003;100:12712-12717.
ABSTRACT | FULL TEXT  

CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina
Mehalow et al.
Hum Mol Genet 2003;12:2179-2189.
ABSTRACT | FULL TEXT  

An unusual retinal vascular morphology in connection with a novel AIPL1 mutation in Leber's congenital amaurosis
Heegaard et al.
Br. J. Ophthalmol. 2003;87:980-983.
ABSTRACT | FULL TEXT  

Study of the involvement of the RGR, CRPB1, and CRB1 genes in the pathogenesis of autosomal recessive retinitis pigmentosa
Bernal et al.
J. Med. Genet. 2003;40:e89-89.
FULL TEXT  

Evidence of autosomal dominant Leber congenital amaurosis (LCA) underlain by a CRX heterozygous null allele
Perrault et al.
J. Med. Genet. 2003;40:e90-90.
FULL TEXT  

Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination
Jacobson et al.
Hum Mol Genet 2003;12:1073-1078.
ABSTRACT | FULL TEXT  

Progession of phenotype in Leber's congenital amaurosis with a mutation at the LCA5 locus
Mohamed et al.
Br. J. Ophthalmol. 2003;87:473-475.
ABSTRACT | FULL TEXT  

Electroretinographic Abnormalities in Parents of Patients With Leber Congenital Amaurosis Who Have Heterozygous GUCY2D Mutations
Koenekoop et al.
Arch Ophthalmol 2002;120:1325-1330.
ABSTRACT | FULL TEXT  

Molecular genetics of Leber congenital amaurosis
Cremers et al.
Hum Mol Genet 2002;11:1169-1176.
ABSTRACT | FULL TEXT  

The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina
van der Spuy et al.
Hum Mol Genet 2002;11:823-831.
ABSTRACT | FULL TEXT  

CRB1 has a cytoplasmic domain that is functionally conserved between human and Drosophila
den Hollander et al.
Hum Mol Genet 2001;10:2767-2773.
ABSTRACT | FULL TEXT  

Implications of Genetic Analysis in Leber Congenital Amaurosis
Gamm and Thliveris
Arch Ophthalmol 2001;119:426-427.
FULL TEXT