Imperial College London

Dr. Anna C. Need

Faculty of MedicineDepartment of Brain Sciences

Honorary Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 8436a.need Website

 
 
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Location

 

7N2aCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Need:2012:10.1136/jmedgenet-2012-100819,
author = {Need, AC and Shashi, V and Hitomi, Y and Schoch, K and Shianna, KV and McDonald, MT and Meisler, MH and Goldstein, DB},
doi = {10.1136/jmedgenet-2012-100819},
journal = {Journal of Medical Genetics},
pages = {353--361},
title = {Clinical application of exome sequencing in undiagnosed genetic conditions},
url = {http://dx.doi.org/10.1136/jmedgenet-2012-100819},
volume = {49},
year = {2012}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BACKGROUND: There is considerable interest in the use of next-generation sequencing to help diagnose unidentified genetic conditions, but it is difficult to predict the success rate in a clinical setting that includes patients with a broad range of phenotypic presentations. METHODS: The authors present a pilot programme of whole-exome sequencing on 12 patients with unexplained and apparent genetic conditions, along with their unaffected parents. Unlike many previous studies, the authors did not seek patients with similar phenotypes, but rather enrolled any undiagnosed proband with an apparent genetic condition when predetermined criteria were met. RESULTS: This undertaking resulted in a likely genetic diagnosis in 6 of the 12 probands, including the identification of apparently causal mutations in four genes known to cause Mendelian disease (TCF4, EFTUD2, SCN2A and SMAD4) and one gene related to known Mendelian disease genes (NGLY1). Of particular interest is that at the time of this study, EFTUD2 was not yet known as a Mendelian disease gene but was nominated as a likely cause based on the observation of de novo mutations in two unrelated probands. In a seventh case with multiple disparate clinical features, the authors were able to identify homozygous mutations in EFEMP1 as a likely cause for macular degeneration (though likely not for other features). CONCLUSIONS: This study provides evidence that next-generation sequencing can have high success rates in a clinical setting, but also highlights key challenges. It further suggests that the presentation of known Mendelian conditions may be considerably broader than currently recognised.
AU - Need,AC
AU - Shashi,V
AU - Hitomi,Y
AU - Schoch,K
AU - Shianna,KV
AU - McDonald,MT
AU - Meisler,MH
AU - Goldstein,DB
DO - 10.1136/jmedgenet-2012-100819
EP - 361
PY - 2012///
SN - 1468-6244
SP - 353
TI - Clinical application of exome sequencing in undiagnosed genetic conditions
T2 - Journal of Medical Genetics
UR - http://dx.doi.org/10.1136/jmedgenet-2012-100819
UR - http://hdl.handle.net/10044/1/41671
VL - 49
ER -