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Mutation Analysis of 3 Genes in Patients With Leber Congenital Amaurosis
Andrew J. Lotery, MD, FRCOphth;
P. Namperumalsamy, MD, MS;
Samuel G. Jacobson, MD, PhD;
Richard G. Weleber, MD;
Gerald A. Fishman, MD;
Maria A. Musarella, MD;
Creig S. Hoyt, MD;
Elise Héon, MD;
Alex Levin, MD;
James Jan, MD;
Byron Lam, MD;
Ronald E. Carr, MD;
Alan Franklin, MD, PhD;
S. Radha, PhD;
Jeaneen L. Andorf, BA;
Val C. Sheffield, MD, PhD;
Edwin M. Stone, MD, PhD
Arch Ophthalmol. 2000;118:538-543.
Objective To assess the frequency of mutations in the CRX, GUCY2D, and RPE65 genes in patients with Leber congenital amaurosis (LCA).
Patients One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from India.
Methods 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.
Results 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.
Conclusions 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.
Clinical Relevance 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.
From the Departments of Ophthalmology and Visual Sciences (Drs Lotery, Franklin, and Stone and Mrs Andorf) and Pediatrics (Dr Sheffield), University of Iowa Hospitals and Clinics, Iowa City; Aravind Eye Hospital, Madurai, India (Drs Namperumalsamy and Radha); Department of Ophthalmology, Scheie Eye Institute, Philadelphia, Pa (Dr Jacobson); Department of Ophthalmology and Molecular and Medical Genetics, Casey Eye Institute, Portland, Ore (Dr Weleber); Department of Ophthalmology and Visual Sciences, University of Illinois Eye and Ear Infirmary, Chicago (Dr Fishman); and Departments of Ophthalmology, Long Island College Hospital, New York, NY (Dr Musarella), University of California, San Francisco(Dr Hoyt), the Eye Research Institute of Canada (Dr Héon) and the Hospital for Sick Children (Dr Levin), Toronto, Ontario, the British Columbia Children's Hospital, Vancouver (Dr Jan), Bascom Palmer Eye Institute, Miami, Fla (Dr Lam), and New York University, New York (Dr Carr).
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