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Background Age-related cognitive decline results in increased difficulty in performing tasks that require memory or rapid information processing. Cognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning. The polygenetic contribution to cognitive resilience requires large data sets for analysis. In addition, longitudinal data is needed to identify individual differences in cognitive performance over time. The UK Biobank cohort of over 500,000 participants over the age of 40 offers the potential to advance research on the genetics and biology of cognitive resilience. Methods We created a longitudinal cognitive resilience phenotype by combining the phenotypic cognitive parameter of current reaction time with a proxy phenotype of education years (EY). We used this resilience phenotype, in genome-wide association studies (GWAS) to identify genes and gene sets that influence the biological pathways involved in resilience. To remove the influence of the EY on the analysis we compared genetic data on participants that displayed resilience to those that showed expected cognitive decline. Results GWAS outputs analysis showed 273 significantly enriched genes for participants that demonstrated resilience. Genotype–tissue expression was significant in brain tissue, particularly in the anterior cingulate cortex, frontal cortex, and hippocampus. Biological Pathway analysis includes synapse, post synaptic density and neuron guidance. Conclusion This analysis shows an association between cognitive resilience and enrichment of neuronal activity. Confirmatory examination of these findings in datasets with strong longitudinal cognitive data, such and the Health and Retirement Study, is ongoing., Introduction Type 1 diabetes (T1D) is a polygenic disease characterised by autoimmune inflammatory destruction of the pancreas and subsequent hyperglycaemia. Several GWAS have identified loci associated with T1D risk, but recent evidence suggests that epigenetic changes in DNA methylation may have a causal role in T1D. Methods To identify potential methylation-based biomarkers of T1D, blood-derived DNA from 250 individuals with ≥15 years duration of T1D was compared to 391 controls with no evidence of diabetes. All individuals were from the British Isles. DNA was bisulphite treated using the EZ DNA Methylation Kit (Zymo). The Infinium HD Methylation Assay MethylationEPIC BeadChips (Illumina) were used to determine the methylation status of >850,000 CpG sites, gene bodies and promoters. Results MethylationEPIC data was analysed using GenomeStudio v2011 and Partek Genomics Suite v7.0. Comparing T1D with controls identified 1,706 CpG sites with significantly different (p±2 fold change). Genes including HLA‐DRB1, HLA‐DQA1 and PLEKHA1 have been previously linked to T1D and contained >2 differently methylated CpG sites ≥p, Introduction Rare diseases (RDs) are a public health priority but their scarcity and diversity leads to a lack of knowledge and expertise. Accurate epidemiological information about RDs is necessary to inform public policy, but without an Irish rare disease registry, there is a dearth of primary data. Methods Collaborative work with Orphanet Coordination derived a global point prevalence of RDs from the ‘Orphanet Epidemiological File’ (http://www.orphadata.org) by selecting RDs described by ‘point prevalence’ from predefined geographic regions, and summing point prevalences. In the National Rare Disease Office, expert opinion and disease-specific publications were used to adapt a ‘high prevalence’ list for Ireland. Results Globally, ‘point prevalence’ describes 5,304 RDs ≥85.9%). The minimum cumulative point prevalence of RDs is 3.5‐5.9% of the population. While globally 84.5% RDs analysed ≥n=3585) had a point prevalence of 1/100,000. To construct a comparable Irish ‘high‐ prevalence’ list, 191 RDs with known prevalence >1/100,000 across all countries were drawn from the global list. A further 147 diseases with possible prevalence >1/100,000 in Ireland due to ethnic, environmental or founder‐effect are currently under consideration for inclusion. Conclusion 3.5%‐5.9% is the first evidence‐based estimate of the global population prevalence of RDs. Creation of an Irish list of high‐prevalence RDs permits development of care pathways and systems that address the needs of the majority of Irish people with RDs. Implementation of RD codification in eHealth Ireland will provide more accurate data., Introduction The acute hepatic porphyrias, including acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HP) along with familial Porphyria Cutanea Tarda (fPCT) are autosomal dominantly inherited disorders affecting key enzymes in the haem biosynthetic pathway. Clinically these disorders may manifest as photosensitive skin lesions (VP, HP and PCT) and/or acute neuropathic episodes (AIP, VP and HP). All demonstrate variable penetrance and expressivity. Thus, while biochemical investigations, including blood, urine and faecal porphyrin analysis, are critical for the diagnosis of active porphyric disease, these investigations may not be sensitive enough to identify presymptomatic variant carriers. Hence molecular genetic analysis has become an important component in kindred follow-up for identifying porphyria susceptibility. Methods The Biochemistry Department, St James’s Hospital, Dublin, has established a molecular diagnostic service based on direct nucleotide sequencing to facilitate diagnosis of genetic susceptibility to AIP, VP, HCP and PCT respectively. Results To date over 30 different genetic variants linked with a porphyria phenotype have been identified in different kindreds including non‐Irish. The spectrum of variants includes missense, nonsense, splice‐site and small insertions and deletions e.g. HMBS ≥R26C, R26H, IVS4+1G>A), PPOX ≥IVS4‐1G>A, Q435X, W427X, A150D, Q375X) and CPO ≥R332Q, R332W, c.1291‐1292 ins TG). In addition, novel variants have been identified in collaboration with Cardiff Porphyria Centre. Conclusion This unique insight into the molecular basis of porphyrias in the ROI indicates that acute porphyrias and fPCT are genetically heterogeneous. Furthermore, the variant scanning assay in St James’s Hospital has identified pathogenic variants in >93% of confirmed porphyria kindreds, Background The developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies which co-present with intellectual disability, and occur in cases without a family history of epilepsy. Their severe phenotype means that DEEs are thought to be primarily monogenic, caused by highly damaging rare mutations. Currently, analysis of exome sequence data can identify a causative mutation in around 40% of DEEs. Little is known about the genetic architecture of the remaining DEEs which screen-negative after genomic analysis. Here, we used a method known as polygenic risk scoring (PRS) to test whether the burden of common genetic variation is relevant to the development of the DEEs. Methods Exome and GWAS data on DEE cases (n=745), and population controls (n=75,000) were obtained from the DDD cohort and Ukbiobank, respectively. Damaging mutations in known epilepsy genes were bioinformatically inferred. PRS were calculated using the most recent ILAE GWAS of epilepsy and compared between i) DEE cases and the general population, and ii) DEE cases with and without damaging mutations. Results DEE cases with and without inferred damaging mutations were found to have elevated PRS for epilepsy. We did not detect a significant difference in PRS between DEE cases with and without damaging mutations. Discussion This research provides the first evidence that common genetic variation contributes to the development of the DEEs. Our results suggest common genetic variation contributes to DEE status irrespective of the presence of a highly damaging rare genetic variant. Further work in additional cohorts is required to extend these results., Rationale The phenotypic features in a person with epilepsy are often complex with regards to seizure presentations, which is acknowledged by the most recent revision of the seizure classification by the International League Against Epilepsy (ILAE). We provide updated seizure-related human phenotype ontology (HPO) terms to facilitate a deep phenotypic interpretation of heretofore unexplained genetic epilepsies. Methods The Epilepsiome project is a Task Force of the Genetics Commission of the ILAE and represent the link to the gene curation efforts within the ClinGen Epilepsy Clinical Domain Working Group (CDWG). Within the efforts to align terminology used in the diagnostic space, the Epilepsiome Project revised HPO terms for epileptic seizures. The updated classification was built through an online portal and consensus was achieved through biweekly conference calls. Results Focal, generalised and neonatal HPO seizure terminologies were constructed according to the most recent ILAE classification and aligned with the existing HPO structure. This ontology allows capture of clinical information at various levels of detail and aims to preserve the onset, awareness and motor/non-motor nature of each seizure type, using multiple parentages. We integrated other frequently observed seizures currently not included in the ILAE, which required a separate branch within the ontology due to biological peculiarity of their age of onset, their clinical significance or genetic architecture. Conclusions Improvements in HPO terms for epileptic seizures will enable a more versatile seizure ontology leading to deep phenotyping of people with epilepsy to improve associations with genomic data in both a research and diagnostic setting., Purpose Target5000 aims to genetically characterise approximately 5000 people in Ireland with an inherited retinal degeneration (IRD). Thus far, over 1,000 IRD patients have been sequenced for variants in 260 IRD genes. One arm of the project focuses on improving detection of candidate variants by whole genome sequencing (WGS), by analysing non-coding mutations and performing functional analysis. Approach IRD patients are clinically diagnosed by Target5000 ophthalmologists. When informed consent is given, the Target5000 study employs target capture next generation sequencing (NGS), with a positive candidate detection rate of 68%. To improve detection rates, whole-gene or WGS was employed on a case-dependent basis to identify pathogenic intronic variants not previously captured. Results One common form of IRD is ABCA4-associated Stargardt disease (STGD1), often caused by deep-intronic variants. Thus far, 36 ‘unresolved’ STGD1 and cone-rod dystrophy cases have undergone targeted ABCA4 whole-gene sequencing, positively identifying a candidate in ~50% of cases. A variant in intron 30 resulting in a pseudoexon inclusion was particularly frequent and found in 5/16 (likely) solved cases. Furthermore, 40 patient samples have undergone WGS. Conclusions An objective of Target5000 is to provide actionable outcomes empowering patients with genetic diagnoses and potentially future access to clinical trials or approved treatments, where appropriate. The results presented highlight the significant value of a target capture NGS strategy as a preliminary diagnostic measure, with remaining elusive cases undergoing more extensive genetic analysis. This methodology improves variant detection rates and progresses the goal of fully elucidating the genetic architecture of IRDs in Ireland., Background Copy Number Variants (CNVs) are large genomic deletions/duplications of >1kb, spanning regions that can encompass one or many genes. Though a common form of structural variation, pathogenic CNVs, of population freq., The Ladakhi people dwell in the Jammu and Kashmir regions of India, between the Karakoram and Himalayan mountain ranges, at ≥3400 meters altitude. The Ladakhi share similar linguistic, cultural and religious practices with Tibetans. However, relative to Tibetans, the Ladakhi are very poorly studied at the level of population structure and genetic selection. In this context, we set out to conduct a genomic survey of population structure in representative samples of the Ladakhi people. Methods We genotyped 310 Ladakhi DNA samples using the Illumina Global Screening Array gene chip. We merged the Ladakhi with data from 800 individuals representing different reference language groups including; Sino-Tibetan (Tibetans, Sherpa, Han), Indo-European (Indo-Aryan, Hazara), Austroasiatic (Munda) and Burusho (a linguistic isolate in Jammu-Kashmir). We performed ADMIXTURE, principal component analysis (PCA), fineSTRUCTURE and ChromoPainter analysis on the combined autosomal data. Results In PCA plots, the Ladakhi population cluster together with Sherpa and Tibetans, forming a distinct Himalayan group, different from other mainland populations of South and East Asia. ADMIXTURE analysis at k=4 suggests ancestry proportions in the Ladakhi to be approximately 50% Highlander (Tibetan/Sherpa) and 50% Indo-European. These results suggest contemporary Ladakhi people are the admixed of Tibetans and Indo-Europeans. Conclusions Our results suggests a considerable component of the Ladakhi genome descends from ancestral highlander populations residing on the Tibetan plateau for the last 35,000 years, with subsequent admixture with neighbouring Indo-European populations., Background The EU recognises rare disease (RD) as life threatening with delays in establishing a diagnosis and treatment. The Irish National Plan for RDs (2014) recommended epidemiological studies of RD prevalence to improve both cost efficiencies and care of patients with RD’s. Objective To derive the incidence of paediatric RD and the number of paediatric RD mortality cases through analysis of records held at two major tertiary paediatric hospitals, for children born in the year 2000. Methods Cases were identified using electronic/manual records from: the National Paediatric Mortality Registry office; Clinical, Cytogenetics and Molecular genetics database; Radiology and the Hospital In-Patient Enquiry system (HIPE). In addition a detailed analysis of national death registration information for RDs from 2006-2016 was undertaken along with a 2year study (2015-2016) of inpatient RD deaths. Results There were 54,789 livebirths in 2000. Genetics records identified 801 cases of RDs Ongoing HIPE searches identified 1381 cases. Mortality data revealed that of all deaths on the Register (2006-2016), (n=4044) aged 0-14, 58.56% (n=2368) had a RD diagnosis with age distribution; Neonates, 56% (1140/2050), Post-neonates, 58% (450/778), Children aged 1-14 years, 64% (778/1216). Of the total (n=234) inpatient deaths with a RD from 2015-2016, 52.6% (n=123) were cared for at the two major centres. Conclusion This study to-date has identified > 2,200 RD patients presenting by age 17 giving a minimum incidence of 4% for paediatric RDs. We expect the final figure to be higher when we complete analysis of all the HIPE and sub-specialty data from these major centres., Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. ADPKD is primarily caused by variants in PKD1 and PKD2. Sequencing of PKD1 is difficult due to multiple pseudogenes. There is unexplained variance in the age-of-onset of PKD, even within families. Aim 1) Establish a targeted NGS panel to improve molecular diagnosis of PKD and 2) characterize large ‘super-families’ for the study of new ADPKD genes and genetic modifiers. Methods NGS was performed using a custom Roche SeqCap targeted panel (273 genes) and Illumina NextSeq. Bioinformatics was performed using an in-house GATK pipeline. Pathogenicity was assigned using American College of Medical Genetics and Genomics guidelines and Mayo Clinic PKD in-house methods. Gap-filling Sanger sequencing was utilized in unsolved cases Results 172 PKD patients were sequenced with average coverage 189X. A molecular diagnosis meeting pathogenicity criteria was obtained in 82% (141/172) of patients following gap-filling Sanger of PKD1 and PKD2 (n=41). 46 of the PKD-causing variants we detected were novel. We identified 13 rare, diagnostic PKD variants shared across multiple affected individuals recorded clinically as having no known familial relationship. Second-degree relatedness was confirmed via clinical follow-up. These families form the basis for the assembly of PKD ‘super-families’. Conclusions NGS is suitable for sequencing of PKD genes including PKD1, although some gap filling by Sanger is required for complete coverage. We have identified 13 potential ADPKD ‘super-families’ using genomic data for further study. These results are improving diagnostics of ADPKD in the Irish renal clinic., Purpose Target5000 is a genetic study to detect and characterise variants associated with inherited retinal degenerations (IRD). Choroideremia is an X-Linked recessive chorioretinal degenerative condition with progressive atrophy of several key cells of the retina and the surrounding blood retinal barrier. Here we describe a novel deletion in the CHM gene found in two Irish pedigrees. This 500kb deletion represents the largest yet detected IRD-associated deletion in Ireland. Approach As part of the Irish IRD registry, Target5000, patients with inherited retinal degenerative conditions are recruited. Target capture sequencing was employed to investigate variation in 254 IRD-associated genes. Upon detection of the deletion in CHM, PCR analysis was used to elucidate the full extent of the deletion. Results Two members of a large X-linked Retinitis Pigmentosa pedigree clinically presented with choroideremia and tested negative for the segregating RPGR variant found in other affected members of this pedigree. Both males were sequenced and found to possess large deletions spanning the CHM gene, totalling 500kb. This deletion has also been detected in a second Irish pedigree since its discovery. Two additional males and two carrier females from this second pedigree were all found to be severely affected with progressive choroideremia. Conclusions Typically, female carriers of CHM mutations show mild stationary signs with no symptoms, while males are severely affected. In this instance, females were more severely affected than expected with advanced signs of degeneration and progressive visual decline. This is possibly due to random X-inactivation and the severity of CHM gene deletion., Introduction The largest cohort of patients at The National Centre for Adult Inherited Metabolic Disorders (NCIMD) have Phenylketonuria (PKU). The NCIMD manages patients transitioned from Paediatric services upon reaching adulthood. Improved treatments have extended life expectancy and increased quality of life for patients with PKU; however diet and supplements remained the only means of treatment for life until the recent introduction of Sapropterin dihydrochloride. Aim To analyse the genotype of the PKU cohort in attendance at The NCIMD with a focus on responsiveness to Sapropterin dihydrochloride. Method The data are collated from when the Adult unit was first established in 2013 until the end of May 2019. Exclusion criteria include patients over the age of 53 and patients who have two negatively indicated genotypes for the use of Sapropterin dihydrochloride. Genotypes are recorded in a secured database onsite and descriptive analyses were performed. Results The total number of patients examined is 282; 104 were male (36.8%) and 178 were female (63.1%). The total samples processed and available for analysis were 148 (male= 46, 31%; female= 102, 68.9%). The frequency of Saptopterin dihydrochloride responsiveness in both alleles was observed (responsive= 15, 10%; unresponsive= 48, 48.33%; uncertain= 85, 57%). The most common alleles recorded were R408W (41.1%), F39L (13.8%), 165T (11.2%), and L249F (3.8%). Conclusion Due to the uncertainty surrounding Sapropterin dihydrochloride responsiveness for various common mutations in the Irish PKU cohort, there is a need for greater genetic and metabolic collaboration. Analysis and treatment may be impacted by time elapsed from sending samples to receiving results., Introduction The Department of Clinical Genetics at CHI provides services for individuals affected by or at risk of a genetic condition in the Republic of Ireland. There are currently 3,283 referrals waiting to be seen, of whom 930 are waiting longer that the HSE standard of 18 months. A negative consequence of a long waiting list is that patients die whilst waiting. Resulting harm includes: 1) no diagnosis 2) no genetic testing, no DNA stored, 3) family unaware of a hereditary disorder, denied screening, 4) relatives having unnecessary screening as no predictive test for family, 5) future pregnancy options limited if paediatric proband undiagnosed. As of 13/06/2019, we have recorded 33 deaths on our waiting list. We began to systematically collect data on deaths since March 2018. This study concentrates on these cases; n=15/33. Aims To identify the consequences to the relatives of these 15 referrals. Results Nine were adult cancer genetic referrals, 5/9 diagnostic, 3/9 predictive, and a further case had NF2. Only 1/9 had DNA stored. Two adult patients had a cardiac family history (Marfan syndrome, cardiomyopathy) respectively. Neither had DNA stored. Four paediatric patients had multiple malformations secondary to a chromosomal or genetic syndrome. In 3/4 a diagnosis had already been reached. The fourth case, who died unexpectedly of unrelated causes, had no DNA stored. Summary 11/15 patients who died did not have DNA stored, precluding diagnosis and risk calculation for their relatives. As each extended 3 generation Irish family has ~64 relatives, lack of diagnosis has far reaching consequences., Background Women who carry a pathogenic variant in either a BRCA1 or BRCA2 gene have a high lifetime risk of developing breast and tubo-ovarian cancer. To manage this risk, women may choose to undergo risk-reducing surgery to remove breast tissue, ovaries and fallopian tubes. Surgery should increase survival, but can impact women’s lives adversely at a psychological and psychosexual level. Interventions to facilitate psychological adjustment and improve quality of life post risk-reducing surgery are needed. Aim of Review To examine psychosocial interventions in female BRCA carriers who have undergone risk-reducing surgery and to evaluate the effectiveness of such interventions on psychological adjustment and quality of life. Methods We searched the Cochrane Central Register of Controlled trials (CENTRAL) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, Web of Science and Scopus up to April 2019. Results We identified two studies; one randomised controlled trial and one nonrandomised study. Conclusions The effect of psychosocial interventions on quality of life and emotional well-being in female BRCA carriers who undergo risk-reducing surgery is uncertain given limited high quality evidence. Next Generation Sequencing, along with targeted cancer treatments, increasing knowledge around the biology of cancers and the results of the 100K Genome Project will open up genetic testing to many more women. For as long as surgical interventions remain the dominant risk-reducing option for management of women with a deleterious BRCA gene, health professionals have a responsibility to ensure there is provision to holistically manage the outcomes of such surgery., Introduction FATCO (Fibular Aplasia, Tibial Campomelia and Oligosyndactyly) syndrome is a rare descriptive diagnosis first defined by Courtens et al. in 2005, who recognised a comparable pattern of malformations with his own case and 4 others described in the literature. Aetiology remains unknown, however defects involved in SHH (Sonic hedgehog) gene expression have been proposed. Case Description We report on a term male infant born with severe malformations. On examination, there was absence of the left radius and ulna, bilateral anterior angulation of lower limbs with skin dimpling overlying. Both ankle joints were dysplastic and there was oligosyndactly of both feet. Right upper limb was normal. X-rays of the limbs revealed dysplastic tibiae, absence of both fibulae, a right foot containing 3 ossified metatarsals with 2 formed digits, and a left foot with a single ossified metatarsal and two soft tissue digits with small bony elements. The infant had no other associated anomalies, and is developmentally appropriate at 1 year. Management included Symes amputation, prosthetics and following genetic referral FATCO syndrome was suggested as the best fitting diagnosis. Whole genome sequencing of the infants blood is currently being performed. Discussion This is an important case to report as there are very few descriptions in the literature, In keeping with the majority of reports, this case appears to be sporadic and development is normal. Our case is male, keeping with preponderance. Treatment aims at optimising functionality of limbs and stabilisations of joints., Introduction Fibrous cephalic plaques (FCP) are a characteristic manifestation of tuberous sclerosis complex (TSC) and occur in one third of cases. Their natural history and long term course is unknown, as is the outcome of long term follow-up of TSC cases in old age. Phenotype and methods We describe an 80 year old with TSC due to a c.2784dupC TSC2 mutation, who was diagnosed in infancy with an FCP and was regularly followed up at the TSC clinic over 8 decades with regular epilepsy treatment and renal monitoring. Results Regular clinical photography and clinical records document the plaque at different ages. The FCP naturally resolved at 74 years. Facial angiofibromas also faded with time in the last decade. His epilepsy and renal abnormalities remained under control with careful surveillance and monitoring. Discussion Natural aging in the eighth decade causes progressive laxity of collagen and leads to natural resolution of FCPs. This novel finding with a unique 80 year follow up yields valuable insights into the aging changes within FCPs and facial angiofibromas as the pathways linking facial angiofibromas and FCP’s through the TGF-β1 pathway are now being elucidated. Conclusion We present a clinical odyssey showing the natural progression and history of FCPs in TSC and comment on the mechanistic pathways allowing potential interventions in this disfiguring condition. TSC cases can be successfully managed and complications – particularly in the brain and kidney, can be avoided over an entire lifetime. This is encouraging for long term prospects for patients with TSC., Introduction Fabry disease is an X-linked inherited disorder due to deficient activity of the enzyme alpha-galactosidase A and progressive lysosomal deposition of globotriaosylceramide in cells. Aim To report the genotype/phenotype landscape of the adult Fabry disease cohort attending The National Centre for Adult Inherited Metabolic Disorders (NCIMD). Method All Fabry patients (N=70) attending NCIMD until end of May 2019 were included in this analysis. Genotypes and phenotypes were recorded by chart review. Descriptive analyses were performed. Result 26 (37.1%) were male (median age 43 [32:54]) and 44 (62.9%) were female (median age 46 [25:61]). The AGAL pathogenic variants were missense (52, 74.3%), deletion (9, 12.9%), nonsense (8, 11.4%) and duplication (1, 1.4%). Most missense variants occurred in exon 2 (25%), exon 3 (19.2%), exon 5 (23.1%) and exon 6 (21.2%). 21.2% of missense variants were N215S. 28 patients were on enzyme therapy and 2 were on oral chaperone therapy. The incidence of cardiac (M=18/26; F=18/44; p=0.021), renal (M=14/26; F=18/44; p=0.304), neurological (M=17/26; F=20/44; p=0.107) and hearing (M=14/26; F=19/44; p=0.399) involvement were observed. Within N215S cohort, 2 had hypertrophic cardiomyopathy and 5 with a degree of left ventricular hypertrophy. Conclusion Pathogenic variants were observed across the AGAL gene in the cohort. Incidence of cardiac involvement in both genders is similar. Females had more frequently observed renal, neurological and hearing involvement. N215S AGAL variant is the most common variant which is associated with a predominant cardiac phenotype, thus collaboration between clinical geneticists and cardiovascular physicians are important when establishing diagnosis and management., Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with a worldwide prevalence of 1:500. Genetic etiology is suspected in up to 50% of HCM patients. To gain insight into the diagnostic yield and mutation spectrum of HCM, a retrospective review was performed for 114 consecutive cases with a clinical suspicion of HCM who underwent multigene panel testing at our laboratory between 2014 and 2019. Method Data was manually extracted from laboratory reports with respect to indication for testing, number of genes on panel, variants identified and classification at the time of testing. Results A total of 114 patients with a diagnosis of HCM had samples submitted for diagnostic testing using a multigene panel of between 16 and 20 genes, depending on the year of testing. 56 patients had no genetic variant identified, 33 patients had a pathogenic or likely pathogenic variant identified and 25 had a variant of uncertain significance identified. One 11 year old patient had a normal result from an 18 gene panel for HCM, but was later diagnosed with Friedrich ataxia. One adult female patient had a normal result from a 19 gene panel but was later diagnosed with Fabry disease. Conclusion Clinically actionable ‘Pathogenic’ or ‘Likely pathogenic’ variants were identified in 29% of patients with a Clinical diagnosis of Hypertrophic Cardiomyopathy with VUS being identified in 22%. The most common 2 genes in which clinically actionable variants were found were MYH7 (47%) and MYBPC3 (31%)., Huntington’s disease (HD) is an inherited progressive neurodegenerative condition. In the Republic of Ireland genetic testing for HD is available via two routes. Symptomatic individuals can access testing via a Neurologist. Asymptomatic individuals with a known family history of HD can seek testing via a genetic counselling multi-step process. Aim The aim of the audit was to review the activity of the HD specialty clinic. Methods Retrospective chart, laboratory and clinical database review for HD referrals received for 2016, 2017 and 2018 was carried out. Parameters examined included: number of referrals, age profile, motivation for testing, results. Results Over this 3 year period 93 referrals were received. 80 referrals were for predictive testing and 13 for genetic counselling post testing through neurology. The youngest person was 18 years of age at time of referral. More females requested a referral for predictive testing than males, 48 (60%) and 32 (40%) respectfully. The most common motivation given for predictive testing was with regard to family planning and concerns for children and to help them plan for the future. Of the 30 tests carried out to date, 52% were mutation positive and 42% were mutation negative. The average age of those who proceeded with testing was 37yrs. Conclusion These findings reflect data published from the UK with regard to age of presentation and female to male bias. The most common motivation for testing was family planning unlike the UK where the most common reason provided was to reduce uncertainty.

Within the framework of the Work Package 5 «Valorisation de l'image des produits aquacoles» and the activity 5.3 «Innovation en vue de valoriser les produits aquacoles» of SecurAqua project, we have assessed the possibility of diversification of Sicilian farmed fish, through the production of processed products, among which seabream fillets hamburgers. In order to verify the feasibility of the process, we have performed a preliminary study of global quality characteristics of the product, including both the nutritional and sensory aspects correlated to the security and sustainability of the product. Results showed that, in terms of nutritional requirements, the hamburger samples maintained the same characteristics of the fresh product, comparable with those of fillets, throughout the whole storage time. Regarding the shelf-life characteristics of the fresh product stored for 15 days in a freezer, sensory analysis suggest a consumption limited to few days from the preparation. Results obtained from this study indicate that hamburgers of Sparus aurata represent a potential new fish product that could satisfy the consumer requests, as well as a new reference commodity related to its usability and its nutritional properties. Experiments are in progress to evaluate the extension of shelf-life through alternative methods of preservation.

Chitin has been extracted from two Tunisian crustacean species. The obtained chitin was transformed into the more useful soluble chitosan. These products were characterized by their biological activity as antimicrobial and antifungal properties. The tested bacterial strains were Escherichia coli American Type Cell Culture (ATCC) 25922, Pseudomonas aeruginosa ATCC 27950 and Staphylococcus aureus ATCC 25923. Four fungi strains were also tested Candida glabrata, Candida albicans, Candidaparapsilensis and Candida kreusei. Squilla chitosan showed a minimum inhibitory concentration (MIC) against the different fungi exceptionally for C. kreusei. Their antioxidant activity was investigated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and inhibition of linoleic acid peroxidation. Parapenaeus longirostris Chitosan showed the highest radical scavenging properties. Chitin and chitosan produced were also characterized with Fourier Transform Infrared Spectroscopy (FTIR).Key words: Antibacterial, antifungal, antioxidant, chitin, chitosan, crustacean.

Les variations des profils éléctrophorétiques des protéines sarcoplasmiques (SPP) et myofibrillaires (MFP) chez les filets de la Dorade royale d’origine sauvage et d’élevage congelés à -18°C ont été suivies durant 4 mois de stockage. A l’état frais, la différence de l’origine de production de la Dorade (sauvage/aquaculture) n’a pas illustré de distinctions particulières dans les profils protéiques des filets. Durant le stockage congelé, l’analyse densitométrique des profils MFP et SPP chez les deux populations de Dorade a permis de discerner des modifications mineures liées à l’origine de production du poisson et à la progression du temps de stockage. Ces faibles changements, notamment dans la fraction MFP, ont été plus précoces chez la Dorade d’élevage. En effet, ces variations ont touché, dès le premier mois de congélation, la densité optique des peptides de faibles poids moléculaires (70, 23, 16 et 10 kDa) de la Dorade d’élevage, alors que les premières modifications touchant les bandes de 75, 60, 37 et 18 kDa chez la Dorade sauvage ont été détectées à partir du deuxième mois de stockage. Les analyses électrophorétiques ont montré que, lors de la congélation, les dorades sauvages sont plus résistantes aux phénomènes de désorganisation et de dénaturation des protéines musculaires que leurs congénères d’élevage. Changes in electrophoretic profiles of sarcoplasmic (SPP) and myofibrillar (MFP) proteins of frozen (-18°C) wild and farmed gilthead sea bream fillets were assessed during 4 months of storage. Initially, no specific distinctions in the protein profiles were found between wild and farmed fresh fish fillets. Throughout frozen storage, densitometric analysis of MFP and SPP profiles showed minor modifications, particularly in MFP fraction, related to the origin of fish and time of storage. Thus, the optical density of farmed fish low molecular weight peptides (70, 23, 16 and 10 kDa) were affected after 1 month of frozen storage, such changes were observed after 2 months in the wild fish bands of 75, 60, 37 and 18 kDa. The electrophoretic analysis showed that wild sea bream fillets were more resistant to muscle protein disorganization and denaturation, occurring during frozen storage, than farmed fish Published Sparus aurata, wild and farmed fish, freezing, protein electrophoresis

La comparaison de la composition biochimique de la chair et des déchets (têtes, queues et carapaces) de Penaeus kerathurus du nord et sud de la Tunisie a été réalisée (protéines totales, lipides totaux, matière sèche, composition en acides gras, azote basique volatil total (ABVT) et acides aminés totaux libres (AATL)). La matière sèche a varié entre 23,77 et 26,06%. Pour tous les échantillons les taux d’ABVT sont restés inférieurs aux seuils limites (20 mg /100g). Les teneurs en acides aminés totaux libres et des lipides des co-produits chez les deux lots de Penaeus kerathurus sont supérieures à celles de la partie consommable. Les acides gras polyinsaturés (AGPI) constituent la partie majeure des acides gras totaux des tissus et co-produits de Penaeus kerathurus des deux régions, suivie par les acides gras saturés (AGS) et monoinsaturés (AGMI). Les acides gras les plus fréquents sont C16:0, C20:5n-3 (EPA), C22:6n-3 (DHA), C18:1n-9, C18:0, C16:1n-7, C20:4 et C18:1n7 تم القيام بدراسة المحتويات البيوكيميائية للحم وفواضل الجمبري) (Penaeus kerathurus (الرأس، الذيل والقشرة) فيما يخص البروتينات، الدهنيات، السكريات، المادة الجافة، الأحماض الدهنية و الازوت القاعدي المتبخر الكامل. لقد تراوحت نسبة المادة الجافة بين % 26.06 – 23.77. كما ظلت نسبة الازوت القاعدي المتبخر الكامل تحت المعدل المسموح 35مغ/100غ. أما في ما يخص الحامض الاميني الكامل السائب و الدهنيات لفواضل الجمبري لكلتي المجموعتين وجدت ارفع من الجزء الذي يستهلك. تمثل الأحماض الدهنية كثيرة عدم التشبع القسط الأكبر من الأحماض الدهنية الكاملة للحم و فواضل (Penaeus kerathurus) بالجهتين مصحوبة بالأحماض الدهنية المشبعة و الأحادية عدم التشبع.من الأحماض الدهنية الأكثر تواجدا 16:0, C20:5n-3 (EPA), .C22:6n-3 (DHA), C18:1n-9, C18:0, C16:1n-7, C20:4 et C18:1n7 Biochemical composition of muscle and processing by-products (heads, shells and tails) of Penaeus kerathurus caught off the north and the south coasts of Tunisia was investigated (Total protein, total lipid, dry matter, fatty acids composition, total volatile basic nitrogen, free amino acids). Dry matter ranged from 23,77 to 26,06%. Total Volatile basic nitrogen (TVBN) of all samples was less than 20mg/ 100g which are thought to be the acceptable limit of marine products. The free amino acids amounts of the processing by-products from two regions were higher than the edible parts. The percentage of polyunsaturated fatty acid was important in the tissues and by-products of both species from both regions. Thus, polyunsaturated fatty acids constitute the major fraction followed by saturated fatty acids and monounsaturated. The main fatty acids in both shrimp species muscle and by-products were C16:0, C20:5n-3, C22:6n-3, C18:1n-9, C18:0, C16:1, C20:4 and C18:1n-7. Published Chair, Déchets, Penaeus kerathurus, composition biochimique

لدراسة تأثير عملية تحويل سمك السردين واللاطشة إلى المعلبات على الجودة الغذائية، قمنا بمتابعة موشرات جودة الدهنيات و تركيبتها من الأحماض الدهنية و أثبتت النتائج أن تغيرات كمية و جودة الدهنيات متعلقة أساسا بتركيبة سمك السردين أو اللاطشة الطازج بالدهنيات و بتركيبة المادة الحافظة (زيت الزيتون أو الطماطم). كما أثبتت التحاليل بواسطة الكروماتوغرافيا ذات الطور الغازي ثراء المعلبات بالأحماض الدهنية التالية C18 :1 ω9 وC18 :2 ω6 . وأخيرا، يمكننا التأكيد أن سمك السردين واللاطشة المعلب بزيت الزيتون و الطماطم غني بالأحماض الدهنية من عائلتيωω3 وω6 . The effects of cooking and sterilisation steps on muscle lipid deterioration of Sardinella aurita and Sardina pilchardus canned in olive oil and tomato sauce respectively were investigated. Lipid contents of Sardinella aurita flesh were significantly affected (p < 0.05) by the canning process. However, lipid levels of Sardina pilchardus remained constant during processing. The peroxide value and thiobarbituric index increased slightly after the cooking step but changed significantly (p < 0.05) following canning. Both canned sardine and sardinella absorbed coating-oil during sterilisation inducing a higher oleic (C18:1 n-9) and linoleic (C18:2 n-6) acids content. Independently of coating-oil category, the eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids concentrations ranged from 3.00 to 6.24% and from 5.12% to 40.26% respectively. Although, lipids of Sardinella aurita and Sardina pilchardus were slightly affected by the canning process, and they remain a good source of ω3 and ω6 fatty acids. Dans le présent travail, les effets de la cuisson et de la stérilisation sur la qualité et la composition en acide gras des lipides de la sardinelle Sardinella aurita et la sardine Sardina pilchardus au cours de la mise en boite dans l’huile d’olive et la sauce de tomate ont été étudiés. La teneur en lipides dans la chair de la sardinelle Sardinella aurita a augmenté significativement (p

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In order to investigate the shelf life of swordfish steaks vacuum-packed with Rosmarinus officinalis, microbiological, chemical and sensorial analyses were carried out after 1, 3, 6, 8, 12 and 16 days of storage. In the treated samples, total volatile bases ranged from 7.35 to 13.05 mg/100 mL and trimethylamine from 1.21 and 7.9 mg/100 g. No significant change in the levels of ninhydrin- positive substances was observed. As regards the biogenic amines (BA), cadaverine increased linearly to 5.6 and 4.8 mg/100 g, and histamine to 4.9 mg/100g and 3.9 mg/100 g in the control and treated sample respectively. As regards the other BAs, no significant differences between the two samples were found. The effects of rosemary were reflected by a lower peroxide value of 2.72 mEq/kg in the treated steaks compared to 3.33 mEq/kg in the control sample at the end of the trial. The initial H2S-producing bacteria and psychrotrophic counts of 3 and 5 log10 cfu/g increased to 5 and 6.2 log10cfu/g after 16 days of storage in the treated samples. Salmonella, Staphylococcus aureus, Escherichia coli and Listeria monocytogenes were not detected in any sample. The addition of rosemary in combination with vacuum packaging extended the shelf life of swordfish steaks by four days.

Cell-based agriculture is an emerging and attractive alternative to produce various food ingredients. In this study, five strains of marine yeast were isolated, molecularly identified and biochemically characterized. Molecular identification was realized by sequencing the DNA ITS1 and D1/D2 region, and sequences were registered in GenBank as Yarrowia lipolytica YlTun15, Rhodotorula mucilaginosa RmTun15, Candida tenuis CtTun15, Debaryomyces hansenii DhTun2015 and Trichosporon asahii TaTun15. Yeasts showed protein content varying from 26% (YlTun15) to 40% (CtTun15 and DhTun2015), and essential amino acids ranging from 38.1 to 64.4% of the total AAs (CtTun15-YlTun15, respectively). Lipid content varied from 11.15 to 37.57% with substantial amount of PUFA (>12% in RmTun15). All species had low levels of Na (

Non-edible parts of crustaceans could be a rich source of valuable bioactive compounds such as the carotenoid astaxanthin and peptides, which have well-recognized beneficial effects. These compounds are widely used in nutraceuticals and pharmaceuticals, and their market is rapidly growing, suggesting the need to find alternative sources. The aim of this work was to set up a pilot-scale protocol for the reutilization of by-products of processed shrimp, in order to address the utilization of this valuable biomass for nutraceutical and pharmaceuticals application, through the extraction of astaxanthin-enriched oil and antioxidant-rich protein hydrolysates. Astaxanthin (AST) was obtained using “green extraction methods,” such as using fish oil and different fatty acid ethyl esters as solvents and through supercritical fluid extraction (SFE), whereas bioactive peptides were obtained by protease hydrolysis. Both astaxanthin and bioactive peptides exhibited bioactive properties in vitro in cellular model systems, such as antioxidant and angiotensin I converting enzyme (ACE) inhibitory activities (IA). The results show higher astaxanthin yields in ethyl esters fatty acids (TFA) extraction and significant enrichment by short-path distillation (SPD) up to 114.80 ± 1.23 µg/mL. Peptide fractions of &lt, 3 kDa and 3–5 kDa exhibited greater antioxidant activity while the fraction 5–10 kDa exhibited a better ACE-IA. Lower-molecular-weight bioactive peptides and astaxanthin extracted using supercritical fluids showed protective effects against oxidative damage in 142BR and in 3T3 cell lines. These results suggest that “green” extraction methods allow us to obtain high-quality bioactive compounds from large volumes of shrimp waste for nutraceutical and pharmaceutical applications.

Background Among the third-generation biodiesel feed stock, oleaginous marine yeasts are the least studied microorganisms for such purpose. Results Wild strains yeasts were isolated from various Tunisian marine sources including fish waste (Candida tenuis CtTun15, Debaryomyces hansenii DhTun2015, Trichosporon asahii TaTun15 and Yarrowia lipolytica YlTun15) and seawater (Rhodotorula mucilaginosa RmTun15). Following incubation with ethyl methanesulfonate (EMS: 75 mM) for various periods of time (T15, T30, T45, T60 min), the cell viability of these strains responded differentially according to yeast species. For instance, mutated CtTun15 did not survive after 30 min of EMS treatment; higher resistances were observed in DhTun2015 (45 min), in YlTun15, RmTun15 and in TaTun15 (60 min) but with significant decreased cell viabilities (survival rate: 6.02, 3.16, 11.22, 11.58, 7.70%, respectively). For all surviving mutated strains, the optima of biomass and lipid yields were detected after 96 h in YPD culture; but derived from strains submitted to different period of EMS incubation. In most mutated strains, the maximum biomass (BP) and lipid (LP) productivities coincided and were observed after 30 min of EMS incubation. Only CtTun15 showed different optima of BP and LP (after 30 min and 15 min, respectively). The fatty acids (FA) compositions considered essential in the prediction of biodiesel criteria; were highly affected by EMS mutagenesis. Essentially, 30- and 45-min EMS incubation induced the highest levels of PUFA and MUFA in YlTun15, RmTun15 and TaTun15 with non-significant differences in the different times. However, CtTun15 and DhTun2015 mutant strains responded differently, with the highest levels of MUFA observed following 15 and 45 min; and that of PUFA after 30 and 45 min, respectively. Conclusion The methyl-esterification of FA from the three mutated yeast strains (30 min—YlTun15, RmTun15 and TaTun15) yielded biodiesel with physical proprieties consistent with the International Standard System. However, investigations are needed for up-scaling biodiesel production.