Mutation analysis of 3 genes in patients with Leber congenital amaurosis

Andrew J Lotery; P Namperumalsamy; Samuel G Jacobson; Richard G Weleber; Gerald A Fishman; Maria A Musarella; Creig S Hoyt; Elise Héon; Alex Levin; James Jan; Byron  Lam; Ronald E Carr; Alan Franklin; S Radha; Jeaneen L Andorf; Val C Sheffield; Edwin M Stone

doi:10.1001/archopht.118.4.538

Back

Mutation analysis of 3 genes in patients with Leber congenital amaurosis

Journal article

Open access

Peer reviewed

Mutation analysis of 3 genes in patients with Leber congenital amaurosis

Andrew J Lotery, P Namperumalsamy, Samuel G Jacobson, Richard G Weleber, Gerald A Fishman, Maria A Musarella, Creig S Hoyt, Elise Héon, Alex Levin, James Jan, …

Archives of ophthalmology (1960), Vol.118(4), pp.538-543

04/2000

DOI: 10.1001/archopht.118.4.538

PMID: 10766140

Files and links (1)

url

https://doi.org/10.1001/archopht.118.4.538View

Published (Version of record) Open Access

Abstract

To assess the frequency of mutations in the CRX, GUCY2D, and RPE65 genes in patients with Leber congenital amaurosis (LCA). One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from India. Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of 3 genes (CRX, GUCY2D, and RPE65) known to be associated with LCA. Of the 176 probands, 28 (15.9%) harbored possible disease-causing mutations. The relative contribution of each gene to the total number of mutations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8%. No patients who harbored mutations in these genes had associated systemic abnormalities. Molecular diagnosis allowed definitive genetic counseling in a family affected with Best disease and LCA. Molecular diagnosis may be of benefit to patients affected with LCA. The relative paucity of mutations found in this study suggests that more LCA-associated genes remain to be discovered. Molecular diagnosis can confirm and clarify the diagnosis of LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations will be established. This will facilitate the counseling of patients on their visual prognosis and the likelihood of associated systemic anomalies.

Optic Atrophies, Hereditary - genetics

Humans

Child, Preschool

Infant

Male

Genetic Counseling

Polymorphism, Single-Stranded Conformational

DNA - analysis

DNA Mutational Analysis

Trans-Activators - genetics

Adult

Female

Blindness - congenital

Eye Proteins - genetics

Optic Atrophies, Hereditary - diagnosis

Child

cis-trans-Isomerases

Carrier Proteins

Blindness - diagnosis

Gene Frequency

Blindness - genetics

Homeodomain Proteins - genetics

Proteins - genetics

Pedigree

Adolescent

Guanylate Cyclase - genetics

Details

Title: Subtitle: Mutation analysis of 3 genes in patients with Leber congenital amaurosis
Creators: Andrew J Lotery - Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City, USA
P Namperumalsamy
Samuel G Jacobson
Richard G Weleber
Gerald A Fishman
Maria A Musarella
Creig S Hoyt
Elise Héon
Alex Levin - Hospital for Sick Children
James Jan
Byron Lam
Ronald E Carr
Alan Franklin
S Radha
Jeaneen L Andorf
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.118(4), pp.538-543
DOI: 10.1001/archopht.118.4.538
PMID: 10766140
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: 04/2000
Academic Unit: Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979939002771

Metrics

19 Record Views

136 Times Cited - Web of Science