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Jennings, Barbara 
ORCID: https://orcid.org/0000-0003-3792-9182, Philpott, Carl ORCID: https://orcid.org/0000-0002-1125-3236, Bhutta, Mahmood, Willis, Gavin, Swan, Daniel, Woods, Jane and Prinsley, Peter
(2018)
A study of the genetics of cholesteatoma through systematic review and whole exome sequencing.
In: European Conference of Human Genetics 2018, 2018-06-16 - 2018-06-19.
(In Press)
Abstract
Introduction: A cholesteatoma is a mass of keratinising epithelium in the middle ear. It is a rare disorder, associated with significant morbidity. Its OMIM entry (#604183) cites minimal evidence for Mendelian inheritance, but we have observed 31 multiply affected families in Norfolk; including individuals with bilateral disease, suggesting a genetic component for its aetiology. Methods: We conducted a systematic literature review (SR) to identify any published studies about the genetics of cholesteatoma and established a national biobank for subsequent whole exome sequencing (WES) studies of familial disease. We have also completed a pilot sequencing study to identify candidate variants that segregate with the disease phenotype (using NimbleGen exome capture; and the Illumina HiSeq4000 platform). Results: In our SR, we identified 8 case-series with multiply-affected families and associations with congenital malformation syndromes. DNA and clinical data have been collected from 42 participants (from 9 multiply affected Norfolk families) to date. In 2018, participants will also be recruited from 10 additional UK centres. Our pilot: WES study of 16 participants from 4 families identified 95,437 variants. Variant filtering, using pedigree analysis, has identified 430 candidate genes for further filtering using the Ensembl Variant Effect Predictor. Conclusion: We have completed our SR (see PROSPERO register CRD42015023579) and established the first biobank to explore the genetics-of-cholesteatoma. A WES strategy and bioinformatics pipeline have been developed in the pilot study; and preliminary filtering has identified candidate variants that could have an impact on TGF β signalling and inflammatory processes.
| Item Type: | Conference or Workshop Item (Other) |
|---|---|
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Groups > Respiratory and Airways Group Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Population Health |
| Related URLs: | |
| Depositing User: | Pure Connector |
| Date Deposited: | 10 May 2018 11:30 |
| Last Modified: | 05 Dec 2023 01:18 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/67021 |
| DOI: |
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