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19Th Meeting of the Irish Society of Human Genetics, Friday 9Th September 2016

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19Th Meeting of the Irish Society of Human Genetics, Friday 9Th September 2016 Ulster Med J 2017;86(1):55-68 Abstracts 19th Meeting of the Irish Society of Human Genetics, Friday 9th September 2016. Belfast City Hospital SPOKEN PAPERS: DM Lambert1, SA Lynch1, R Marron1, D Gray2, EP Treacy1. S01. Deep phenotyping and genomic analysis for Behcet’s 1National Rare Disease Office, Mater Misericordiae Hospital, disease Dublin 7, 2National Clinical Programme for Rare Diseases, RCPI. A Coleman1, F McKinley2, A Gough2, N Wheatley2, H Xu3, AJ The National Rare Disease Office (NRDO), initiated in June 2015, McKnight1. collates and disseminates Irish rare disease (RD) information. The prevalent nature of RD (1 in 16 of the population, approximately 1 2 Centre for Public Health, Queen’s University of Belfast, Behcets 80% of which has a genetic basis) and the burden to the health care 3 UK, Centre for Experimental Medicine, Queen’s University of system is under-recognised and a neglected public health issue. Belfast. Awareness of rare diseases is a challenge, especially for GPs who each care for > 90 RD patients. Behcet’s disease (BD) is a complex, multifactorial rare disease, which is poorly understood. Genetic and environmental factors The NRDO has made 58 presentations, lectures and publications contribute to BD, but the process of diagnosis is challenging with and received numerous enquiries (58% of contacts from patients/ inconsistent clinical manifestations. A recent survey of individuals families, 25% from health care professionals and 4% researchers). living with rare disease(s) in Northern Ireland revealed ~50% of Mapping Irish RD clinical and research expertise is developing 1 individuals receive ≥1 misdiagnosis with /20 seeing >10 doctors. through Orphanet Ireland. Enrolment of clinical expert centres has increased by 50%,but only <10% of the most prevalent RDs Individuals with BD report a range of symptoms, which are are represented. This reflects well-developed services for some variable in onset, severity, and frequency for this systemic conditions, (e.g. vasculitis and ALS), but more disparate services vasculitis. Patients describe prolonged journeys to diagnosis with for others (intellectual disability and multisystemic RD). A lack of multiple healthcare professionals and medical specialties; there is coding and/or registries makes it difficult to identify rare patients no BD specialist in Northern Ireland. Using invitations via social within hospital systems. Numerous cross-border initiatives seek to media, voluntary groups, and direct contact we are using surveys maximize clinical and research outcomes through collaboration. incorporating micro-narratives, one-to-one semi-structured However, < 1% of Irish RD research and <30% of RD clinical interviews, and focus groups to collect detailed family histories trials are registered on Orphanet. For European recognition and and stressor information to help characterise recurrent features in participation, Ireland must make its RD research visible, and ‘count’ patients living with BD and their relatives in Northern Ireland. RD patients and activity. Irish patients will be disadvantaged unless BD is most often reported in populations along the Silk Road. we develop systems to prepare for entry to European Reference The highest prevalence is reported in Turkey at 20-420/100,000, Networks and become “trial ready”. While progress is slow, these compared 1.5/100,000 individuals in the UK. Mapping through are early days and we are optimistic about future developments. general practitioners revealed a much higher than expected S03. PTEN Hamartoma Tumour Syndrome Screening Audit – prevalence of 12.6/100,000 in the Northern Ireland population. Northern Ireland 2016 Clusters were observed in Co. Down and Co. Antrim and plotted with social-demographic information. This high ‘UK’ prevalence RS Moore1, V McConnell1. and the identification of several families with multiple members diagnosed makes NI ideal to explore genetic and epigenetic risk 1Clinical Genetics Department, Belfast City Hospital, 51 Lisburn factors for BD. Road, Belfast BT9 7AB. This project involves deep phenotyping and strategies to improve Aims: To assess the tumour surveillance advice given to patients recognition of Behcet’s disease, build collaborative partnerships, in Northern Ireland with confirmed PTEN hamartoma tumour improve data collection, enhance training, and information sharing. syndrome (HTS). S02. Capturing Irish Rare Disease activity, a must for improved Methods: We used the surveillance advice laid out by the Pan cross border care and research Thames Cancer Genetics Group in 2014 to benchmark our UMJ is an open access publication of the Ulster Medical Society (http://www.ums.ac.uk). The Ulster Medical Society grants to all users on the basis of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence the right to alter or build upon the work non-commercially, as long as the author is credited and the new creation is licensed under identical terms. 56 The Ulster Medical Journal patients against. A coding search was carried out on our regional previously reported in literature to be associated aggressive MTC information management system to identify all patients with a presentation, yet remains untested for in the routine diagnosis confirmed diagnosis. The written/ electronic notes of these patients of MTC. Supported by findings from shallow whole genome were reviewed. We adhered to the National PTEN audit inclusion sequencing, we report for the first time in thyroid cancer, the criteria of including patients older than16 years, those with a occurrence of a catastrophic “chromothripsis-like pattern” (CTLP) pathogenic/likely pathogenic PTEN mutation or at 50% risk and event, which involved shattering of chromosome 4 leading to those who had received advice between 01/08/10 - 01/08/2015. complete abrogation of normal chromosomal function, in addition to dramatic wide-spread copy number aberrations (CNA), across Results: 21 patients were identified. All patients had a pathogenic both primary tumour and bone marrow samples. We further PTEN mutation. 6 children were excluded. 1 adult was excluded describe the presence of loss-of-heterozygosity (LOH) in key genes due to lack of documented advice. 6 patients had a cancer diagnosis. involved in DNA repair mechanism pathways such as ATM, which 9 patients had a positive family history of cancer. Annual breast possibly facilitated the CTLP event, in addition to LOH in other screening was recommended for 67% of patients which involved disease-associated genes such as ALK and NOTCH1 as key drivers mammography in 83% and MRI in 17%. Annual thyroid USS and of the aggressive and rapidly fatal clinical course in this patient and TFTs were recommended for 54% and 31% of patients respectively. unresponsiveness to the standard-of-care targeted agent chosen. 16% of female patients had gynaecology referrals completed. Given a possible rapid generation of tumor neo-antigens as a result An annual dermatological review was recommended for 23% of of the CTLP event, immunotherapy may have been more suitable patients. Widely variable colonoscopy and renal USS screening as a treatment option. Moreover, the presence of disease-associated was recommended for 77% and 65% of patients respectively. No SNP’s within the RET proto-oncogene, support their inclusion as cases of Lhermitte-Duclos disease were identified vs 12% in the part of routine RET genetic testing for aggressive MTC cases. national UK audit. These results provide a rationale for application of comprehensive genomic analysis of cancers presenting with unusually aggressive Conclusions: There is a need for regional PTEN tumour behavior to facilitate more appropriate therapeutic options and surveillance guidelines to be produced and implemented through a diagnoses. regional PTEN specialist clinic. S05. Target 5000: Genetic characterisation of a cohort of S04. Post-mortem examination of an aggressive case of inherited retinal degeneration (IRD) patients medullary thyroid carcinoma characterized by catastrophic genomic abnormalities A Dockery1, M Carrigan1, C Malone2, D Keegan3, K Stevenson3, J Silvestri4, A Green5, J McCourt6, P Humphries1, PF Kenna1,2, GJ D Kelly1,2*, S Das3,4*, B Moran3,4*, K Han2,5, N Mulligan2,5, C Farrar1. Barrett2,5, PG Buckley6, P Mc Mahon1,2, J McCaffrey1,2, HF Van 7 3,4 7 8 3 Essen , K Connor , B Ylstra , D Lambrechts , WM Gallagher , 1The School of Genetics & Microbiology, Trinity College Dublin, 3,4§ 1,2§ DP O’Connor , CM Kelly *Equal Contribution, § Senior co- Dublin 2, Ireland, 2Royal Victoria Eye and Ear Hospital, Dublin authors. 2, Ireland, 3The Mater Misericordiae Hospital, Dublin 7, Ireland, 4The Royal Victoria Hospital, Belfast, Northern Ireland, 5Our 1Department of Medical Oncology, Mater Misericordiae Lady’s Children’s Hospital, Crumlin, Dublin, Ireland, 6RCSI University Hospital, Eccles St. Dublin 7. 2Conway Institute, Clinical Research Centre, Smurfit Building, Beaumont Hospital, University Hospital Dublin, Belfield, Dublin 4, Ireland. 3Cancer Beaumont Road, Dublin 9, Ireland. Biology and Therapeutics lab, Conway Institute, University 4 College Dublin, Belfield, Dublin 4, Ireland. Department of The Target 5000 research project aims to provide genetic testing Molecular and Cellular Therapeutics, Royal College of Surgeons for the estimated 5,000 people in Ireland who have an inherited 5 in Ireland, 123 St. Stephens Green, Dublin 2, Ireland. Department retinal condition. Many clinical trials are available for patients of cellular pathology,
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