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Mutation analysis of 3 genes in patients with Leber congenital amaurosis

Mutation analysis of 3 genes in patients with Leber congenital amaurosis
Mutation analysis of 3 genes in patients with Leber congenital amaurosis
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.
0003-9950
538-543
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Namperumalsamy, P.
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Jacobson, Samuel G.
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Weleber, Richard G.
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Fishman, Gerald A.
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Musarella, Maria A.
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Hoyt, Creig S.
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Héon, Elise
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Levin, Alex
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Jan, James
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Lam, Byron
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Carr, Ronald E.
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Franklin, Alan
cdb3ba43-5383-4ed1-9d83-c25c0b1e0277
Radha, S.
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Andorf, Jeaneen L.
fecdc4d7-f5c0-44aa-a674-00450cd1148a
Sheffield, Val C.
c1a1f2fe-b32b-494e-bd82-b1d90c0563fa
Stone, Edwin M.
545dc2cf-5ba2-4c9d-95aa-e22218c323c5
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Namperumalsamy, P.
e6ec9b3c-e9aa-4ce4-90a6-213ad1018c04
Jacobson, Samuel G.
4f5c2f74-c431-4ca1-aaa5-848e3ead0695
Weleber, Richard G.
662a5221-fd3c-4de3-b52d-53b72fce2105
Fishman, Gerald A.
5d293c00-72e2-41eb-b321-81149756ec6a
Musarella, Maria A.
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Hoyt, Creig S.
00a38ea7-3db0-4d88-be22-fb24108524c1
Héon, Elise
0d4c27a1-cd38-4f57-90a3-5344457bd572
Levin, Alex
449e1ab0-f7dd-4869-83eb-451b38675718
Jan, James
2543e9ff-d96c-4640-94bc-b929e0db2d09
Lam, Byron
8c7c07d7-32dc-4dcb-a1cc-dbc61ba342d3
Carr, Ronald E.
a5f807b2-ce6e-4060-8a98-e6676709bef1
Franklin, Alan
cdb3ba43-5383-4ed1-9d83-c25c0b1e0277
Radha, S.
a9305a7e-586f-4cdd-a442-854df6db14b2
Andorf, Jeaneen L.
fecdc4d7-f5c0-44aa-a674-00450cd1148a
Sheffield, Val C.
c1a1f2fe-b32b-494e-bd82-b1d90c0563fa
Stone, Edwin M.
545dc2cf-5ba2-4c9d-95aa-e22218c323c5

Lotery, Andrew J., Namperumalsamy, P., Jacobson, Samuel G., Weleber, Richard G., 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. and Stone, Edwin M. (2000) Mutation analysis of 3 genes in patients with Leber congenital amaurosis. Archives of Ophthalmology, 118 (4), 538-543. (doi:10.1001/archopht.118.4.538). (PMID:10766140)

Record type: Article

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.

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.

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Published date: April 2000
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 359193
URI: https://eprints.soton.ac.uk/id/eprint/359193
ISSN: 0003-9950
PURE UUID: 5ebb93ce-ad1c-4dc4-ad84-8f57160b33d3
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 01 Nov 2013 15:39
Last modified: 31 Jan 2019 01:36

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Contributors

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

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