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Mutations in the CRB1 gene cause Leber congenital amaurosis

Mutations in the CRB1 gene cause Leber congenital amaurosis
Mutations in the CRB1 gene cause Leber congenital amaurosis
OBJECTIVES: 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. PATIENTS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. CLINICAL RELEVANCE: 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
cohort, prognosis, infant, polymerase chain reaction, mutation, us government, genotype, optic atrophies, congenital, genes, genetics, hereditary, adolescent, pathology, analysis, chemistry, dna, research support, humans, cohort studies, child, adult, proteins, blindness, single-stranded conformational, protein, phs, methods, drosophila proteins, phenotype, non-us government, diagnosis, middle aged, hypothesis, visual acuity, membrane proteins, preschool, polymorphism, counseling, dna primers, patients
0003-9950
415-420
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Jacobson, Samuel G.
4f5c2f74-c431-4ca1-aaa5-848e3ead0695
Fishman, Gerald A.
5d293c00-72e2-41eb-b321-81149756ec6a
Weleber, Richard G.
662a5221-fd3c-4de3-b52d-53b72fce2105
Fulton, Anne B.
c9b24b3c-1e01-4c5a-8c2e-b3c6687c3a9c
Namperumalsamy, P.
e6ec9b3c-e9aa-4ce4-90a6-213ad1018c04
Heon, Elise
6bb59d5b-80e5-404b-8775-41195a0d6d84
Levin, Alex V.
02a06985-b2c7-483b-9d75-7eff3755e915
Grover, Sandeep
a8eb4564-60c3-4fbb-8139-6533ae052633
Rosenow, Justin R.
5822719a-00eb-406f-b6eb-0f6fe88ba95d
Kopp, Kelly K.
78b35997-bd75-4dca-95ec-9e64caf509a1
Sheffield, Val C.
c1a1f2fe-b32b-494e-bd82-b1d90c0563fa
Stone, Edwin M.
545dc2cf-5ba2-4c9d-95aa-e22218c323c5
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Jacobson, Samuel G.
4f5c2f74-c431-4ca1-aaa5-848e3ead0695
Fishman, Gerald A.
5d293c00-72e2-41eb-b321-81149756ec6a
Weleber, Richard G.
662a5221-fd3c-4de3-b52d-53b72fce2105
Fulton, Anne B.
c9b24b3c-1e01-4c5a-8c2e-b3c6687c3a9c
Namperumalsamy, P.
e6ec9b3c-e9aa-4ce4-90a6-213ad1018c04
Heon, Elise
6bb59d5b-80e5-404b-8775-41195a0d6d84
Levin, Alex V.
02a06985-b2c7-483b-9d75-7eff3755e915
Grover, Sandeep
a8eb4564-60c3-4fbb-8139-6533ae052633
Rosenow, Justin R.
5822719a-00eb-406f-b6eb-0f6fe88ba95d
Kopp, Kelly K.
78b35997-bd75-4dca-95ec-9e64caf509a1
Sheffield, Val C.
c1a1f2fe-b32b-494e-bd82-b1d90c0563fa
Stone, Edwin M.
545dc2cf-5ba2-4c9d-95aa-e22218c323c5

Lotery, Andrew J., Jacobson, Samuel G., Fishman, Gerald A., Weleber, Richard G., Fulton, Anne B., Namperumalsamy, P., Heon, Elise, Levin, Alex V., Grover, Sandeep, Rosenow, Justin R., Kopp, Kelly K., Sheffield, Val C. and Stone, Edwin M. (2001) Mutations in the CRB1 gene cause Leber congenital amaurosis. Archives of Ophthalmology, 119 (3), 415-420.

Record type: Article

Abstract

OBJECTIVES: 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. PATIENTS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. CLINICAL RELEVANCE: 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

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More information

Published date: March 2001
Keywords: cohort, prognosis, infant, polymerase chain reaction, mutation, us government, genotype, optic atrophies, congenital, genes, genetics, hereditary, adolescent, pathology, analysis, chemistry, dna, research support, humans, cohort studies, child, adult, proteins, blindness, single-stranded conformational, protein, phs, methods, drosophila proteins, phenotype, non-us government, diagnosis, middle aged, hypothesis, visual acuity, membrane proteins, preschool, polymorphism, counseling, dna primers, patients

Identifiers

Local EPrints ID: 59997
URI: http://eprints.soton.ac.uk/id/eprint/59997
ISSN: 0003-9950
PURE UUID: 14cc2ec4-ab44-47c6-818a-ede7258c5be6
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 02 Sep 2008
Last modified: 09 Jan 2022 03:12

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Contributors

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

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