European journal of medical genetics最新文献

{"title":"Mutation spectrum of Tyrosinemia type I in Iran, A retrospective cohort study","authors":"Zahra Beyzaei ,&nbsp;Zahra Goudarzi ,&nbsp;Seyed Mohsen Dehghani ,&nbsp;Hossein Moravej ,&nbsp;Mohammad Hadi Imanieh ,&nbsp;Maryam Ataollahi ,&nbsp;Mozhdeh Heidari ,&nbsp;Bita Geramizadeh","doi":"10.1016/j.ejmg.2024.104970","DOIUrl":"10.1016/j.ejmg.2024.104970","url":null,"abstract":"<div><p>Hereditary Tyrosinemia Type 1 (HT1) is a genetic disorder characterized by an autosomal recessive inheritance pattern, caused by mutations in the fumarylacetoacetate hydrolase (<em>FAH</em>) gene, which results in a deficiency of fumarylacetoacetase. In our study, we identified a total of 15 mutations, including 12 newly discovered and 3 previously reported pathogenic mutations, in a cohort of 19 Iranian patients with the acute form of HT1. Out of the 12 novel variants identified, 11 were missense variants: p.Asp126His, p.Gln75Glu, p.Leu385Pro, p.Ser92Thr, p.Leu96Arg, p.Val167Glu, p.Ala94Asp, p.Gly353Trp, p.Ser164Pro, p.Glu86His and p.Ala163Pro. Additionally, there was one nonsense variant, p.Try244X, that had not been previously reported. Interestingly, the Arg237X variant was found to be particularly prevalent in this study. Notably, three exons, namely exons 9, 3, and 6, exhibited a higher frequency of mutations. All of the identified variants are presumed to result in loss of function, impacting the clinical signs, disease progression, increasing tyrosine level, and the specific location of the mutation. Our study has provided valuable insights into the mutation spectrum of variants associated with HT1 disease which is reported for the first time from Iran. This information can facilitate the development of targeted mutation screening protocols, focusing on the most prevalent mutations within specific regions or ethnic groups.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104970"},"PeriodicalIF":1.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000624/pdfft?md5=2ff717015c567d947ff336c82e8aaf24&pid=1-s2.0-S1769721224000624-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biallelic potential disease-causing missense variants in TAF1A in two siblings with infantile restrictive cardiomyopathy","authors":"Nan Jiang ,&nbsp;Wenyuan Xu ,&nbsp;Aliaa Abdelhakim ,&nbsp;Anastasiya Matveyenko ,&nbsp;Matthias Szabolcs ,&nbsp;William C. Copeland ,&nbsp;Michele Disco ,&nbsp;Alejandro Iglesias ,&nbsp;Teresa M. Lee ,&nbsp;Ali Naini ,&nbsp;Mythily Ganapathi","doi":"10.1016/j.ejmg.2024.104968","DOIUrl":"10.1016/j.ejmg.2024.104968","url":null,"abstract":"<div><p><em>TAF1A</em>, a gene encoding a TATA-box binding protein involved in ribosomal RNA synthesis, is a candidate gene for pediatric cardiomyopathy as biallelic <em>TAF1A</em> variants were reported in two families with affected individuals. Here, we report a third family with two siblings who presented with infantile restrictive cardiomyopathy and carried biallelic missense variants in <em>TAF1A</em> (NM_001201536.1:c.1021G&gt;A p.(Gly341Arg) and c.781A&gt;C p.(Thr261Pro)). Additional shared clinical features in the siblings included feeding intolerance, congenital leukoencephalopathy, ventriculomegaly and concern for primary immunodeficiency. The first-born sibling passed away at 6 months of age due to complications of hemophagocytic lymphohistiocytosis (HLH) whereas the second sibling underwent cardiac transplantation at 1 year of age and is currently well. We compare the clinical and molecular features of all the <em>TAF1A</em> associated cardiomyopathy cases. Our study adds evidence for the gene-disease association of <em>TAF1A</em> with autosomal recessive pediatric cardiomyopathy.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104968"},"PeriodicalIF":1.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000600/pdfft?md5=1959d5f52aa2dc3b3ac19996e8660d8d&pid=1-s2.0-S1769721224000600-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital clubbing without hypoxia for lysinuric protein intolerance","authors":"Daisuke Watanabe ,&nbsp;Yuko Tsujioka ,&nbsp;Daisuke Nakato ,&nbsp;Mamiko Yamada ,&nbsp;Hisato Suzuki ,&nbsp;Takuma Ohnishi ,&nbsp;Naotaka Tamai ,&nbsp;Toshihide Kijima ,&nbsp;Toshiki Takenouchi ,&nbsp;Fuyuki Miya ,&nbsp;Satoshi Narumi ,&nbsp;Kenjiro Kosaki","doi":"10.1016/j.ejmg.2024.104967","DOIUrl":"10.1016/j.ejmg.2024.104967","url":null,"abstract":"<div><p>Digital clubbing is characterized by bulbous enlargement of the terminal segments of the fingers. Hypotheses including hypoxia have been proposed for the pathogenesis of digital clubbing, but the exact pathogenesis of digital clubbing is still uncertain. Lysinuric protein intolerance (LPI) is caused by pathogenic variants in <em>SLC7A7</em> and is often associated with interstitial lung disease. Previously two patients of LPI with digital clubbing but without hypoxia have been reported. It is unclear whether digital clubbing in LPI is secondary to hypoxia or directly related to SLC7A7 deficiency. Here we report a 6-year-old Japanese boy presented with digital clubbing without hypoxia. He had episodic vomiting, each episode consisting of a single vomiting event occurring once a month, and his growth had been delayed. He had interstitial lung disease and hepatomegaly. He had compound heterozygous pathogenic variants in the <em>SLC7A7</em>, leading to the diagnosis of LPI. Together with the two previously reported patients mentioned above, we conclude that digital clubbing can occur in the absence of hypoxia. Digital clubbing in the absence of hypoxia has been observed in two genetic disorders related to prostaglandin (PG) E2, <em>HPGD</em> and <em>SLCO2A1</em>. PGE2 synthesis is primarily regulated by the cyclooxygenase 2, which plays a critical role in the control of inflammation. A high urine PGE level in the patient was compatible with the notion that PGE2 production may be increased in LPI. The occurrence of digital clubbing in the absence of hypoxia in LPI patients with <em>SLC7A7</em> may be attributed to the mechanism of increased PGE2 production.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104967"},"PeriodicalIF":1.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000594/pdfft?md5=4840da5efaafd99cd62004e70f0a1188&pid=1-s2.0-S1769721224000594-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141990764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The first Brazilian clinical report of Kleefstra syndrome, including semicircular canals agenesis as a possible phenotype expansion","authors":"Eduardo Da Cás ,&nbsp;Lucas V.L. Pires ,&nbsp;Bianca D.W. Linnenkamp ,&nbsp;Marcella C. Allegro ,&nbsp;Rachel S. Honjo ,&nbsp;Débora R. Bertola ,&nbsp;Hiromi Aoi ,&nbsp;Naomichi Matsumoto ,&nbsp;Chong Ae Kim","doi":"10.1016/j.ejmg.2024.104966","DOIUrl":"10.1016/j.ejmg.2024.104966","url":null,"abstract":"<div><h3>Objective</h3><p>to report the first case series of Brazilian children diagnosed with Kleefstra syndrome, present a possible phenotype expansion to the syndrome and to raise physicians' awareness for this rare disease.</p></div><div><h3>Results</h3><p>seven patients with confirmed KS were evaluated, including 5 males and 2 females. Abnormal prenatal findings were observed in 4 patients. Most patients were born at term, with normal birth measurements. All patients had neurodevelopmental delay and 6 evolved with intellectual disability. Hearing loss was present in 57.1% of patients and 28.7% had congenital heart disease. In males, cryptorchidism was present in 75%. Despite the facial dysmorphisms, only 2 out of 7 patients had a pre-test clinical suspicion of KS. One specific patient presented bilateral agenesis of the semicircular canals, a very rare ear manifestation in Kleefstra syndrome, representing a possible phenotype expansion of the syndrome.</p></div><div><h3>Conclusion</h3><p>this report aims to promote awareness among physicians evaluating patients in a context of neurodevelopmental delay or congenital malformations, especially congenital heart defects. We also highlight a possible phenotype expansion of the syndrome, with a case of semicircular anomaly, not reported in this syndrome so far.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104966"},"PeriodicalIF":1.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000582/pdfft?md5=371bdbb5d8d212248eacb6a51f55b3fc&pid=1-s2.0-S1769721224000582-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The history of the international rare diseases research consortium (IRDiRC) and its conferences","authors":"","doi":"10.1016/j.ejmg.2024.104935","DOIUrl":"10.1016/j.ejmg.2024.104935","url":null,"abstract":"<div><p>Individual researchers and consortia have been studying rare diseases for several decades. However, the rare disease community can be very fragmented mainly due to the large heterogeneity of rare diseases. Indeed, for many diseases, there is a very limited amount of researchers and resources available. Concerted efforts to organize the rare disease community and funding were emerging in several countries but so far, international coordination was rather limited. The International Rare Diseases Research Consortium (IRDiRC) aims to correct this. A part of this requires bringing rare disease researchers together for an international conference.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104935"},"PeriodicalIF":1.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000272/pdfft?md5=91fd47c80bcc2493bcaf40d58874aae5&pid=1-s2.0-S1769721224000272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular abnormalities in patients with SHANK3 pathogenic variants: Beyond neurodevelopmental disorders and epilepsy","authors":"Roger Esmel-Vilomara ,&nbsp;Lucy Dougherty-De Miguel ,&nbsp;Alícia Artigas-Baleri ,&nbsp;Eulàlia Turón-Viñas ,&nbsp;Ivon Cuscó ,&nbsp;Asunción Díaz-Gómez ,&nbsp;Luisa Panadés-De Oliveira ,&nbsp;Rodrigo Rocamora ,&nbsp;Susana Boronat","doi":"10.1016/j.ejmg.2024.104965","DOIUrl":"10.1016/j.ejmg.2024.104965","url":null,"abstract":"<div><p>Neurodevelopmental disorders have been linked to numerous genes, particularly pathogenic variants in genes encoding postsynaptic scaffolding proteins, like <em>SHANK3</em>. This study aims to provide insights into the cardiovascular profile of patients with pathogenic <em>SHANK3</em> variants, expanding beyond the well-established associations with neurodevelopmental disorders and epilepsy. We conducted a prospective study involving patients affected by neurodevelopmental disorders with pathogenic <em>SHANK3</em> variants. Comprehensive cardiovascular assessments were performed and molecular genetic testing included chromosomal microarray followed by clinical exome sequencing. We identified five patients with <em>de novo SHANK3</em> variants, all of whom exhibited cardiac involvement, including myocardial dysfunction, congenital heart disease (patent ductus arteriosus), and a case of postictal atrial fibrillation. Our findings emphasize an elevated risk of cardiovascular abnormalities in patients with <em>SHANK3</em> pathogenic variants compared to prior reports. Despite their young age, these patients displayed significant cardiac abnormalities. The study highlights the necessity of integrating cardiac evaluation and ongoing cardiovascular monitoring into multidisciplinary care, facilitating early detection of heart failure and assessment of the risk of sudden unexpected death in epilepsy (SUDEP). Further research is needed to elucidate the underlying mechanisms of cardiac manifestations in <em>SHANK3</em> mutation carriers.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104965"},"PeriodicalIF":1.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000570/pdfft?md5=a1784ad42810e49b34751a97798e94bb&pid=1-s2.0-S1769721224000570-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demystifying gene(tic) therapies","authors":"Chun-Hung Chan ,&nbsp;David A. Pearce","doi":"10.1016/j.ejmg.2024.104963","DOIUrl":"10.1016/j.ejmg.2024.104963","url":null,"abstract":"<div><p>This article summarizes the discussion from a session entitled “Demystifying gene therapies” that was held at the joint RE(ACT) congress and IRDiRC conference, 14–15 March 2023 in Berlin, Germany. The focus of this session was to discuss the changing landscape of genetic therapies and whether current resources exist to provide adequate education to stakeholders, such as researchers, clinicians, patient advocates, legislators, as well as the patients and their families. The goal of this article is not to provide a comprehensive overview of the current landscape in genetic therapies, but rather to highlight resources that may be useful to help “demystify” the myriad of genetic therapeutic approaches.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104963"},"PeriodicalIF":1.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000557/pdfft?md5=03051b5d5212d03cc724e72f838a6890&pid=1-s2.0-S1769721224000557-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic spectrum in Weiss-Kruszka syndrome caused by ZNF462 variants: Three new patients and literature review","authors":"Liselot van der Laan ,&nbsp;Lotte Kleinendorst ,&nbsp;Johanna M. van Hagen ,&nbsp;Quinten Waisfisz ,&nbsp;Mieke M. van Haelst","doi":"10.1016/j.ejmg.2024.104964","DOIUrl":"10.1016/j.ejmg.2024.104964","url":null,"abstract":"<div><p>Weiss-Kruszka Syndrome (WSKA) is caused by pathogenic variants in <em>ZNF462</em> representing a rare autosomal dominant congenital anomaly syndrome. It is characterized by global developmental delay, hypotonia, feeding difficulties, and craniofacial abnormalities, documented in fewer than 30 patients. ZNF462, located on chromosome 9p31.2, is a transcription factor and has an important role during embryonic development and chromatin remodelling. Here, we report three new patients with WSKA, Through whole exome sequencing (WES) analysis, we identified two novel variants in three patients, two of whom are siblings. These variants (c.3078dup, p.Val1027Cysfs5 and c.4792A &gt; T p.Lys1598*) in the <em>ZNF462</em> gene are likely resulting in haploinsufficiency. Our patients help to further delineate the phenotype, genotype and potential therapeutic management strategies for WSKA. Since we report a second WSKA patient with an autoimmune disease further clinical and functional studies are needed to elucidate the association between this chromatin remodelling disorder and the development of autoimmune problems. In the future, collaborative efforts are encouraged to develop an episignature for WSKA, given the gene's function and associated patient phenotypes. This new technology has the potential to provide valuable insights into the disorder.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104964"},"PeriodicalIF":1.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000569/pdfft?md5=e7c37a65efc47c0282bc4bdaa4ba0bc4&pid=1-s2.0-S1769721224000569-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with gilbert and crigler-Najjar II syndrome","authors":"Lina Wu ,&nbsp;Zhenkun Li ,&nbsp;Yi Song ,&nbsp;Yanmeng Li ,&nbsp;Wei Zhang ,&nbsp;Xuemei Zhong ,&nbsp;Xiaoming Wang ,&nbsp;Jian Huang ,&nbsp;Xiaojuan Ou","doi":"10.1016/j.ejmg.2024.104962","DOIUrl":"10.1016/j.ejmg.2024.104962","url":null,"abstract":"<div><p>The spectrum of UDP-glucuronosyltransferase (<em>UGT1A1</em>) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual <em>UGT1A1</em> variants in GS and CNS-II remains to be clarified. To explore the <em>UGT1A1</em> variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected for screening variants in the gene <em>UGT1A1</em> by a polymerase chain reaction and Sanger sequencing. The correlation between different <em>UGT1A1</em> variants and clinical phenotypes was analyzed. A total of 21 <em>UGT1A1</em> variants were identified, including nine novel variants, and constituted 42 <em>UGT1A1</em> genotypes in the GS and CNS-II patients. The most common <em>UGT1A1</em> variants were A (TA)₇TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A (TA)₇TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of <em>UGT1A1</em>, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A (TA)₇TAA, homozygous p.G71R, compound heterozygous A (TA)₇TAA/p.G71R and A (TA)₇TAA/p.P364L, and combined heterozygous A (TA)₇TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A (TA)₇TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A (TA)₇TAA/p.G71R, single heterozygous A (TA)₇TAA, single heterozygous p.G71R, and homozygous A (TA)₇TAA. The spectrum of <em>UGT1A1</em> genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of <em>UGT1A1</em>.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104962"},"PeriodicalIF":1.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000545/pdfft?md5=9e77faf37264755b09f453e41e49702e&pid=1-s2.0-S1769721224000545-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attitudes towards disclosure of familial genetic risk in a Mediterranean island population – A survey of the Maltese population","authors":"Dillon Mintoff ,&nbsp;Bettina Booker ,&nbsp;Shannon Debono ,&nbsp;Matthias Farrugia ,&nbsp;Nikolai Paul Pace","doi":"10.1016/j.ejmg.2024.104961","DOIUrl":"10.1016/j.ejmg.2024.104961","url":null,"abstract":"<div><p>Germline genetic testing has implications that extend beyond the individual patient to relatives, particularly for high-penetrance variants implicated in hereditary cancer or neurodegenerative syndromes. Many countries encourage patient-led communication to inform at-risk relatives, although the efficacy and uptake of this approach varies. Alternative scenarios envisage direct contact mediated by clinicians. The familial disclosure of sensitive genetic information is also determined by complex socio-ethnic factors. To date, no study has explored whether relatives would want to be informed of familial genetic risk and their preferences on different methods of communication in Malta. We thus used a published instrument that utilizes hypothetical scenario methodology to survey the attitudes of the Maltese population (n = 334) to receiving genetic information from family members. Two vignettes on Huntington's disease and colorectal cancer were presented. We also explored preferences towards the communication of genetic risk, confidentiality, and disclosure policies. Our preliminary results show that most respondents want to be informed of their increased risk by a family member or a clinician and would opt to receive confirmatory genetic testing. Most respondents preferred being informed of genetic risk by a close relative, but in the case of non-disclosure would want to be informed by a clinician. Most respondents expressed preference in favour of the introduction of registries, legislative change and sharing of contact details to address cases of nondisclosure. Our findings contribute further to evidence that supports, in selected hypothetical scenarios, an envisioned change in disclosure of genetic data policy by the public that is different from current practice to date.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104961"},"PeriodicalIF":1.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000533/pdfft?md5=32967b439a1a6a2379787c84851abf01&pid=1-s2.0-S1769721224000533-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}