A study of the genetics of cholesteatoma through systematic review and whole exome sequencing

Jennings, Barbara, Philpott, Carl, 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)

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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
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Depositing User: Pure Connector
Date Deposited: 10 May 2018 11:30
Last Modified: 29 Jun 2021 23:47
URI: https://ueaeprints.uea.ac.uk/id/eprint/67021

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