Mutation analysis of 3 genes in patients with Leber congenital amaurosis

Andrew J. Lotery, P. Namperumalsamy, Samuel G. Jacobson, Richard 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

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

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. Result: 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.

Original languageEnglish (US)
Pages (from-to)538-543
Number of pages6
JournalArchives of Ophthalmology
Volume118
Issue number4
StatePublished - Apr 2000
Externally publishedYes

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Leber Congenital Amaurosis
Mutation
Genes
Genetic Counseling
Mutation Rate
DNA Sequence Analysis
Counseling
India
Genotype
Phenotype

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Lotery, A. J., Namperumalsamy, P., Jacobson, S. G., Weleber, R., Fishman, G. A., Musarella, M. A., ... Stone, E. M. (2000). Mutation analysis of 3 genes in patients with Leber congenital amaurosis. Archives of Ophthalmology, 118(4), 538-543.

Mutation analysis of 3 genes in patients with Leber congenital amaurosis. / Lotery, Andrew J.; Namperumalsamy, P.; Jacobson, Samuel G.; Weleber, Richard; Fishman, Gerald A.; Musarella, Maria A.; Hoyt, Creig S.; Héon, Elise; Levin, Alex; Jan, James; Lam, Byron; Carr, Ronald E.; Franklin, Alan; Radha, S.; Andorf, Jeaneen L.; Sheffield, Val C.; Stone, Edwin M.

In: Archives of Ophthalmology, Vol. 118, No. 4, 04.2000, p. 538-543.

Research output: Contribution to journalArticle

Lotery, AJ, Namperumalsamy, P, Jacobson, SG, Weleber, R, Fishman, GA, Musarella, MA, Hoyt, CS, Héon, E, Levin, A, Jan, J, Lam, B, Carr, RE, Franklin, A, Radha, S, Andorf, JL, Sheffield, VC & Stone, EM 2000, 'Mutation analysis of 3 genes in patients with Leber congenital amaurosis', Archives of Ophthalmology, vol. 118, no. 4, pp. 538-543.
Lotery AJ, Namperumalsamy P, Jacobson SG, Weleber R, Fishman GA, Musarella MA et al. Mutation analysis of 3 genes in patients with Leber congenital amaurosis. Archives of Ophthalmology. 2000 Apr;118(4):538-543.
Lotery, Andrew J. ; Namperumalsamy, P. ; Jacobson, Samuel G. ; Weleber, Richard ; Fishman, Gerald A. ; Musarella, Maria A. ; Hoyt, Creig S. ; Héon, Elise ; Levin, Alex ; Jan, James ; Lam, Byron ; Carr, Ronald E. ; Franklin, Alan ; Radha, S. ; Andorf, Jeaneen L. ; Sheffield, Val C. ; Stone, Edwin M. / Mutation analysis of 3 genes in patients with Leber congenital amaurosis. In: Archives of Ophthalmology. 2000 ; Vol. 118, No. 4. pp. 538-543.
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abstract = "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. Result: 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.",
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AU - Fishman, Gerald A.

AU - Musarella, Maria A.

AU - Hoyt, Creig S.

AU - Héon, Elise

AU - Levin, Alex

AU - Jan, James

AU - Lam, Byron

AU - Carr, Ronald E.

AU - Franklin, Alan

AU - Radha, S.

AU - Andorf, Jeaneen L.

AU - Sheffield, Val C.

AU - Stone, Edwin M.

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