Mutations in the CRB1 gene cause Leber congenital amaurosis


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.

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Description/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

Item Type: Article
ISSNs: 0003-9950 (print)
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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, research support, cohort studies, child, adult, proteins, blindness, single-stranded conformational, protein, phs, methods, drosophila proteins, child, phenotype, non-us government, diagnosis, middle aged, hypothesis, visual acuity, membrane proteins, preschool, polymorphism, counseling, dna primers, patients
Subjects: R Medicine > RE Ophthalmology
Q Science > QH Natural history > QH301 Biology
Divisions: University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
University Structure - Pre August 2011 > School of Medicine > Human Genetics
ePrint ID: 59997
Date Deposited: 02 Sep 2008
Last Modified: 27 Mar 2014 18:42
URI: http://eprints.soton.ac.uk/id/eprint/59997

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