Evidence map›Paper›PMID 28005406›Full record

ArticleGenetic testing and molecular biomarkers2017

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses.

Hema L Ramkumar, Harini V Gudiseva, Kameron T Kishaba, John J Suk, Rohan Verma, Keerti Tadimeti, John A Thorson, Radha Ayyagari

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PubMed Full text at PMC Publisher
In one paragraph

Article in Genetic testing and molecular biomarkers, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact, top 90% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Hema L Ramkumar1 Shiley Eye Institute, Jacobs Retina Center, University of California , San Diego, La Jolla, California.
Harini V Gudiseva1 Shiley Eye Institute, Jacobs Retina Center, University of California , San Diego, La Jolla, California.
Kameron T Kishaba1 Shiley Eye Institute, Jacobs Retina Center, University of California , San Diego, La Jolla, California.
John J Suk1 Shiley Eye Institute, Jacobs Retina Center, University of California , San Diego, La Jolla, California.
Rohan Verma1 Shiley Eye Institute, Jacobs Retina Center, University of California , San Diego, La Jolla, California.
Keerti Tadimeti1 Shiley Eye Institute, Jacobs Retina Center, University of California , San Diego, La Jolla, California.
John A Thorson2 Department of Pathology, University of California , San Diego, La Jolla, California.
Radha Ayyagari1 Shiley Eye Institute, Jacobs Retina Center, University of California , San Diego, La Jolla, California.
University of California, San Diego · US

Funding

Molecular Basis of Hereditary Retinal DegenerationsR01EY021237 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AYYAGARI, RADHA · 2011 to 2020
$5.6M
NEI NIH HHS R01 EY021237
6 · The paper itself

Abstract

aimTo test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD).

methodsAfter genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT).

resultsOf the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1).

conclusionsTargeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.

Indexed as

ATP-Binding Cassette TransportersBestrophinsChloride ChannelsDNA Mutational AnalysisExonsEye ProteinsFemaleGenetic Association StudiesGenetic CounselingGenetic TestingHeterozygoteHumansMaleMolecular Diagnostic TechniquesMutationPeripherinsABCA4 protein, humanATP-Binding Cassette TransportersBEST1 protein, humanBestrophinsChloride ChannelsEye ProteinsPeripherinsPRPH2 protein, humanTIMP3 protein, humanTissue Inhibitor of Metalloproteinase-3DNA testinginherited retinal degenerationmolecular diagnosisretinal dystrophyretinitis pigmentosatargeted genetic testing

Identifiers

PMID28005406
PMCPMC5327051
OpenAlexW2564150367

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.