Mutations in the CRB1 gene cause Leber congenital amaurosis

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

doi:10.1001/archopht.119.3.415

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Mutations in the CRB1 gene cause Leber congenital amaurosis

Journal article

Open access

Peer reviewed

Mutations in the CRB1 gene cause Leber congenital amaurosis

Andrew J Lotery, Samuel G Jacobson, Gerald A Fishman, Richard G. Weleber, Anne B Fulton, P Namperumalsamy, Elise Héon, Alex V Levin, Sandeep Grover, Justin R Rosenow, …

Archives of ophthalmology (1960), Vol.119(3), pp.415-420

03/2001

DOI: 10.1001/archopht.119.3.415

PMID: 11231775

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Abstract

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. 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. 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. 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). 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. 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.

Polymerase Chain Reaction

Mutation

Drosophila Proteins

Optic Atrophies, Hereditary - genetics

Membrane Proteins - genetics

Humans

Middle Aged

Child, Preschool

Infant

Optic Atrophies, Hereditary - pathology

DNA Primers - chemistry

Visual Acuity

Blindness - genetics

Polymorphism, Single-Stranded Conformational

DNA - analysis

Adolescent

Adult

Blindness - congenital

Child

Cohort Studies

Details

Title: Subtitle: Mutations in the CRB1 gene cause Leber congenital amaurosis
Creators: Andrew J Lotery - Department of Ophthalmology and Visual Sciences, The University of Iowa College of Medicine, 200 Hawkins Dr, Iowa City, IA 52242, USA
Samuel G Jacobson
Gerald A Fishman
Richard G. Weleber
Anne B Fulton
P Namperumalsamy
Elise Héon
Alex V Levin
Sandeep Grover
Justin R Rosenow
Kelly K Kopp
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.119(3), pp.415-420
DOI: 10.1001/archopht.119.3.415
PMID: 11231775
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Grant note: EY05627 / NEI NIH HHS EY10539 / NEI NIH HHS
Language: English
Date published: 03/2001
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980295102771

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