Linked Life Data

19431183

Source:http://linkedlifedata.com/resource/pubmed/id/19431183

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-7-28
pubmed:abstractText
To assist in distinguishing disease-causing mutations from nonpathogenic polymorphisms, we developed an objective algorithm to calculate an "estimate of pathogenic probability" (EPP) based on the prevalence of a specific variation, its segregation within families, and its predicted effects on protein structure. Eleven missense variations in the RPE65 gene were evaluated in patients with Leber congenital amaurosis (LCA) using the EPP algorithm. The accuracy of the EPP algorithm was evaluated using a cell-culture assay of RPE65-isomerase activity The variations were engineered into plasmids containing a human RPE65 cDNA and the retinoid isomerase activity of each variant was determined in cultured cells. The EPP algorithm predicted eight substitution mutations to be disease-causing variants. The isomerase catalytic activities of these RPE65 variants were all less than 6% of wild-type. In contrast, the EPP algorithm predicted the other three substitutions to be non-disease-causing, with isomerase activities of 68%, 127%, and 110% of wild-type, respectively. We observed complete concordance between the predicted pathogenicities of missense variations in the RPE65 gene and retinoid isomerase activities measured in a functional assay. These results suggest that the EPP algorithm may be useful to evaluate the pathogenicity of missense variations in other disease genes where functional assays are not available.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-10090910, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-11095629, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-11462243, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-12367507, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-12590612, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-14532273, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-14971589, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-16096063, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-16116091, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-16754667, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-17504753, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-17964524, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-18033691, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-18421352, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-18722466, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-18951437, http://linkedlifedata.com/resource/pubmed/commentcorrection/19431183-9326941
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1098-1004
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1183-8
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Predicting the pathogenicity of RPE65 mutations.
pubmed:affiliation
Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural