European journal of medical genetics最新文献

{"title":"ASXL1-related Bohring-Optiz syndrome complicated by persistent neonatal pulmonary hypertension and abnormal alveoli formation","authors":"Makoto Arioka ,&nbsp;Shinji Nakamura ,&nbsp;Katsufumi Nishioka ,&nbsp;Kota Inoue ,&nbsp;Yasuhiro Nakao ,&nbsp;Yumi Miyai ,&nbsp;Hirosuke Morita ,&nbsp;Kosuke Koyano ,&nbsp;Toshiki Takenouchi ,&nbsp;Saneyuki Yasuda ,&nbsp;Yoichi Chiba ,&nbsp;Takashi Iwase ,&nbsp;Masaki Ueno ,&nbsp;Takashi Kusaka","doi":"10.1016/j.ejmg.2024.104978","DOIUrl":"10.1016/j.ejmg.2024.104978","url":null,"abstract":"<div><div>Bohring-Opitz syndrome (BOS) is a rare disease with a characteristic facial appearance and limb position. This report describes a case of BOS complicated by persistent pulmonary hypertension of the newborn (PPHN) and formation of abnormal alveoli that was confirmed by autopsy. A female neonate was born by cesarean section at 37 weeks and 2 days of gestation and found to have a nevus flammeus, exophthalmos, abnormal palate, retraction of the mandible, and a posture characteristic of BOS. The patients had severe PPHN requiring inhalation of nitric oxide. Genetic testing revealed a <em>de novo</em> frameshift variant in <em>ASXL1</em>. Autopsy revealed that the lung was at the saccular stage, equivalent to 28–34 weeks of gestation. This is the first report to present pathological evidence of immaturity of the lung that may be associated with PPHN in a patient with BOS caused by a variant in <em>ASXL1</em>.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104978"},"PeriodicalIF":1.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460955","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":"Exploring the clinical spectrum of CNTNAP2-related neurodevelopmental disorders: A case series and a literature appraisal","authors":"Giulia Barcia ,&nbsp;Giovanna Scorrano ,&nbsp;Marlène Rio ,&nbsp;Cyril Gitiaux ,&nbsp;Marie Hully ,&nbsp;Karine Poirier ,&nbsp;Claude Besmond ,&nbsp;Arnold Munnich ,&nbsp;Nathalie Boddaert ,&nbsp;Nicole Chemaly ,&nbsp;Rima Nabbout","doi":"10.1016/j.ejmg.2024.104979","DOIUrl":"10.1016/j.ejmg.2024.104979","url":null,"abstract":"<div><div>Biallelic pathogenic variants in <em>CNTNAP2</em>, a gene encoding the contactin-associated protein-like 2, have been reported in patients with various clinical presentations including intellectual disability (ID), autistic spectrum disorders (ASD), psychiatric disorders, and focal epilepsy rarely associated to focal cortical dysplasia.</div><div>We report four children carrying novel biallelic <em>CNTNAP2</em> pathogenic variants. They present global developmental delay, psychiatric disorders, and focal epilepsy. All patients displayed brain MRI abnormalities consistent with focal temporal dysplasia. One patient had a temporal resection before the availability of genetic testing. Focal cortical dysplasia represents a frequent finding related to focal refractory epilepsy in <em>CNTNAP2</em> affected patients, and surgery seems to be ineffective in this setting. The genetic testing could therefore be impactful on treatment choices in refractory focal epilepsies.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104979"},"PeriodicalIF":1.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460956","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":"Telehealth for rare disease care, research, and education across the globe: A review of the literature by the IRDiRC telehealth task force","authors":"Faye H. Chen ,&nbsp;Adam L. Hartman ,&nbsp;Mary Catherine V. Letinturier ,&nbsp;Victoria Antoniadou ,&nbsp;Gareth Baynam ,&nbsp;Lara Bloom ,&nbsp;Marco Crimi ,&nbsp;Maria G. Della Rocca ,&nbsp;Giuseppe Didato ,&nbsp;Sofia Douzgou Houge ,&nbsp;Anneliene Jonker ,&nbsp;Martina Kawome ,&nbsp;Friederike Mueller ,&nbsp;James O'Brien ,&nbsp;Ratna Dua Puri ,&nbsp;Nuala Ryan ,&nbsp;Meow-Keong Thong ,&nbsp;Birutė Tumienė ,&nbsp;Melissa A. Parisi","doi":"10.1016/j.ejmg.2024.104977","DOIUrl":"10.1016/j.ejmg.2024.104977","url":null,"abstract":"<div><div>The International Rare Diseases Research Consortium (IRDiRC) Telehealth (TH) Task Force explored the use of TH for improving diagnosis, care, research, and education for rare diseases (RDs). The Task Force reviewed related literature published from January 2017 to August 2023, and identified various models and implementation strategies of TH for RD. The Task Force highlighted the reported value and benefits of using TH for RDs, along with the limitations and opportunities. The number of publications sharply increased since 2021, coinciding with the onset of the COVID-19 pandemic, which forced the rapid adoption of TH in many healthcare settings. One of the major benefits of TH for RDs lies in its capacity to surmount geographical barriers, which helps in overcoming the constraints posed by limited numbers and geographical dispersion of specialists. This was evident during the pandemic when TH was used to maintain a level of continued medical care and research when face-to-face visits were severely restricted. TH, through which clinical research can be decentralized, can also facilitate and enhance RD research by decreasing burden, expanding access, and enhancing efficiency. This will be especially beneficial when coupled with the adoption of digital health technologies, such as mobile health (mHealth) and wearable devices for remote monitoring (i.e., surveillance of outpatient data transmitted through devices), along with big data solutions. TH has also been shown to be an effective means for RD education and peer mentoring, enabling local health care providers (HCPs) to care for RD patients, which indirectly ensures that RD patients get the expertise and multidisciplinary care they need. However, limitations and weaknesses associated with using TH for RD care and research were also identified, including the inability to perform physical examinations and build relationships with HCPs. Therefore, TH has been recommended as a complement to, rather than substitute for, face-to-face consultations. There is also a concern that TH may lead to an amplification of health disparities and inequities related to social determinants of health for those with RDs due to lack of access to TH technologies, inadequate digital literacy, and geographical, socio-cultural, and linguistic barriers. Finally, the Task Force also discussed evidence and knowledge gaps that will benefit from future research efforts to help advance and expand the use of TH for RD care, research, and education.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104977"},"PeriodicalIF":1.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389041","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":"Lessons learned from the RE(ACT) conference on medical devices for rare diseases","authors":"Anneliene H. Jonker ,&nbsp;Tim Buckinx ,&nbsp;Lucia Pannese ,&nbsp;Paulien Klap ,&nbsp;José-Alain Sahel ,&nbsp;Marc Dooms","doi":"10.1016/j.ejmg.2024.104976","DOIUrl":"10.1016/j.ejmg.2024.104976","url":null,"abstract":"<div><div>The field of rare disease therapeutics has witnessed significant growth in recent years, highlighting the need for diverse therapeutic approaches to cater to the unique needs of individuals with rare diseases. Rare disease therapies encompass a broad spectrum of interventions, including orphan medicinal products, orphan medical devices, rehabilitative therapies, and digital therapeutics, with the lines between these categories blurring. This paper covers the session of the RE (ACT)-IRDiRC Conference 2023 and delves into the landscape of orphan medical device research and development, shedding light on the challenges and opportunities in this burgeoning field. It provides a short overview of the different international legislations in the field. In addition, it highlights several exemplary orphan medical devices. The first example is an exoskeleton for boys with Duchenne Muscular Dystrophy, enabling them to maintain arm functionality and independence. Another example presented was an EEG device linked to an app detecting seizures in rare epilepsy conditions, which alerts caregivers to seizures in real-time but also facilitates objective seizure reporting for clinicians, aiding in diagnosis and treatment optimization. It also showcases the role of gamification and enabling technologies in addressing rare diseases, by showing a game designed for children with cystic fibrosis, and a telemedicine system for rehabilitation therapy. Both solutions aim to improve patients' understanding of their conditions and enhance their self-management. In conclusion, this paper underscores the critical need for patient-centric orphan and pediatric medical devices to provide therapeutic options for individuals with rare diseases. It highlights the impact of existing devices on enhancing the quality of life for rare disease patients and emphasizes the necessity for greater incentives and support for research and development in this field.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104976"},"PeriodicalIF":1.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389040","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":"A novel germline Pregnane X Receptor (PXR) variant predisposing to Hodgkin lymphoma in two siblings","authors":"Khusan Khodzhaev ,&nbsp;Tugce Sudutan ,&nbsp;Yucel Erbilgin ,&nbsp;Merve Saritas ,&nbsp;Gulcin Yegen ,&nbsp;Ceyhun Bozkurt ,&nbsp;Muge Sayitoglu ,&nbsp;Rejin Kebudi","doi":"10.1016/j.ejmg.2024.104975","DOIUrl":"10.1016/j.ejmg.2024.104975","url":null,"abstract":"<div><div>Hodgkin's lymphoma (HL) is the most common cancer in adolescents and young adults. A family history of HL increases the risk of developing HL in other family members. Identification of genetic predisposition variants in HL is important for understanding disease aetiology, prognosis, and response to treatment. Aberrant activation of the NF-κB pathway is a hallmark feature of HL, contributing to the survival and proliferation of the malignant cells' characteristic of HL.</div><div>The family with multiple consanguineous marriages with siblings of diagnosed HL was examined by whole-exome sequencing. We found a germline homozygous variation in the PXR ligand binding domain (NM_003889.3:c.811G&gt;A, p.(Asp271Asn)), which was classified as pathogenic by prediction tools and segregated in HL cases. Increased <em>PXR</em> expression was found in homozygous variant carriers compared to heterozygous carriers by quantitative real time PCR (qRT-PCR) and immunofluorescence staining of patients' formalin-fixed paraffin-embedded tissues showed upregulation of PXR, particularly in Hodgkin Reed/Sternberg (HRS) cells.</div><div>Patients with homozygous <em>PXR</em> variant showed significantly high expression compared to <em>PXR</em> wild-type HL, heterozygous and controls (p = 0.0001, p = 0.0004 and p = 0.0001, respectively). <em>PXR</em> homozygous HRS cells had significantly higher PXR expression compared to <em>PXR</em> wild-type HRS cells (p &lt; 0.0001, 3.27-fold change). Albeit PXR's prominent expression in cytoplasm of HRS cells, homozygous <em>PXR</em> HRS cells showed increased PXR expression in nucleus (p &lt; 0.001).</div><div>PXR is a member of the nuclear receptor superfamily and previous studies have demonstrated a pleiotropic effect of PXR on malignant transformation. Expression analysis showed that cell proliferation, apoptosis and inflammation related genes were deregulated, in homozygous <em>PXR</em> HL cases. This study provided clinical evidence to previously reported <em>Sxr</em>^{<em>−/−</em>} mice model that develop multifocal lymphomas, had an aberrantly increased NF-κB expression and consistent inflammation. Further functional studies are needed to elucidate the exact mechanisms of action of PXR in HL pathogenesis.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104975"},"PeriodicalIF":1.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344065","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":"ITGB4-Related pyloric atresia without epidermolysis in two siblings","authors":"Lamiya Aliyeva ,&nbsp;Serdar Beken ,&nbsp;Hanifenur Mancilar ,&nbsp;Eda Albayrak ,&nbsp;Ayse Korkmaz ,&nbsp;Burak Tander ,&nbsp;Yasemin Alanay","doi":"10.1016/j.ejmg.2024.104971","DOIUrl":"10.1016/j.ejmg.2024.104971","url":null,"abstract":"<div><div>Pyloric atresia is a rare gastrointestinal anomaly with an incidence of 1/100,000 in live births. It is usually seen as an isolated condition or in combination with other congenital or hereditary anomalies. Autosomal recessive inherited either fatal or non-fatal variants of pyloric atresia with epidermolysis bullosa are known due to mutations in <em>ITGA6</em>, <em>ITGB4,</em> and <em>PLEC</em> genes. <em>ITGB4</em> gene mutation was recently identified in 5 siblings in 2 families associated with familial isolated pyloric atresia. Herein, we present two siblings who had pyloric atresia together with a homozygous variant in the <em>ITGB4</em> gene and without epidermolysis bullosa. The development of isolated familial pyloric atresia without epidermolysis bullosa may occur due to homozygous variants of the <em>ITGB4</em> gene. Detection of more variants in this gene may help to establish a genotype-phenotype correlation and may suggest the <em>ITGB4</em> gene in patients who have pyloric atresia without epidermolysis bullosa.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104971"},"PeriodicalIF":1.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344066","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":"Exploring Kleefstra syndrome cohort phenotype characteristics: Prevalence insights from caregiver-reported outcomes","authors":"Tanja Zdolšek Draksler ,&nbsp;Arianne Bouman ,&nbsp;Alenka Guček ,&nbsp;Erik Novak ,&nbsp;Pauline Burger ,&nbsp;Florent Colin ,&nbsp;Tjitske Kleefstra","doi":"10.1016/j.ejmg.2024.104974","DOIUrl":"10.1016/j.ejmg.2024.104974","url":null,"abstract":"<div><p>Kleefstra syndrome (KLEFS1) is a rare genetic neurodevelopmental disorder affecting multiple body systems. It continues to be under-researched, and its prevalence remains unknown. This paper builds on the international KLEFS1 cohort of 172 individuals based on the caregiver-reported outcomes collected within the online data collection platform GenIDA and reports the occurrence, frequency and severity of symptoms in KLEFS1. The study clearly shows the importance of caregiver-reported outcomes collections in the rare disease domain. Moreover, the study emphasizes the need for more specific and enhanced data collection methods, suggesting recommendations to optimize caregiver-reported registries and foster an even more profound understanding of rare diseases.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104974"},"PeriodicalIF":1.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000661/pdfft?md5=e94c78b3aeabf529c0f697b4bc6baa91&pid=1-s2.0-S1769721224000661-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239254","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":"Novel CTR9 germline pathogenic splice site variant in siblings with Wilms tumor from Tanzania","authors":"Ali Iman ,&nbsp;Esther Majaliwa ,&nbsp;Lossim G. Kambainei ,&nbsp;Alex Mremi ,&nbsp;Arjen R. Mensenkamp ,&nbsp;Ben C. Hamel","doi":"10.1016/j.ejmg.2024.104973","DOIUrl":"10.1016/j.ejmg.2024.104973","url":null,"abstract":"<div><div>Wilms tumor is the most common childhood renal malignancy. Though mostly non-genetic, it can be syndromic with the involvement of many Wilms tumor predisposing genes and non-syndromic with the involvement of four genes: <em>WT1</em>, <em>REST, TRIM28,</em> and <em>CTR9</em>. Familial and bilateral Wilms tumors do occur, but these are rare. So far, four Wilms tumor families with pathogenic variants in the <em>CTR9</em> gene have been described, all (presumably) inherited from unaffected fathers, and three leading to deletion of exon 9. We are reporting female siblings, of whom one has a bilateral Wilms tumor, with a novel pathogenic splice site variant in the <em>CTR9</em> gene, leading to deletion of exon 9, and inherited from their asymptomatic father. The loss of heterozygosity in the tumor was confirmed. In conclusion, <em>CTR9</em> pathogenic variants are a very rare cause of Wilms tumors and typically result in familial Wilms tumors.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104973"},"PeriodicalIF":1.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S176972122400065X/pdfft?md5=70b5699e9b0e63dd77631839ef4ead00&pid=1-s2.0-S176972122400065X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282353","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":"Two families with spondylo-epi-metaphyseal dysplasia due to compound heterozygocity in the vWFA domain of MATN3","authors":"Tae-Joon Cho ,&nbsp;Hyeran Lee ,&nbsp;Jung Min Ko ,&nbsp;Mihyun Song ,&nbsp;Chang-Ho Shin ,&nbsp;Hae Ryong Song ,&nbsp;Ok-Hwa Kim","doi":"10.1016/j.ejmg.2024.104972","DOIUrl":"10.1016/j.ejmg.2024.104972","url":null,"abstract":"<div><p>Heterozygous variants of <em>MATN3</em> is one of the common causes of multiple epiphyseal dysplasia (MED). Here we report three individuals from two unrelated families who harbor compound heterozygous variants in <em>MATN3</em> (p.Arg121Trp and p.Val220Ala). Contrary to the MED phenotype, these individuals exhibit spondyloepimetaphyseal dysplasia (SEMD) resembling the phenotypes caused by homozygous <em>MATN3</em> variants. Clinical manifestations included short stature, aggravating genu varum, joint laxity, and spinal abnormalities. Radiographic findings were distinct from typical MED. These compound heterozygous variants in the von Willebrand factor A domain of <em>MATN3</em> expand the phenotypic spectrum associated with <em>MATN3</em>, and suggest that extreme MATN3 dysfunction resulting from dual variants can lead to a specific pattern of SEMD.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104972"},"PeriodicalIF":1.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000648/pdfft?md5=a3e0a2d5fd5456fb9607145433c071bc&pid=1-s2.0-S1769721224000648-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239622","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":"Economic evaluation of extended panel analysis in cancer patients with historical NHS diagnostic germline genetic testing – A modeling study based on real-world data","authors":"Qin Xi ,&nbsp;Rahul Patel ,&nbsp;Thomas Linton-Willoughby ,&nbsp;John Short ,&nbsp;Marc Tischkowitz ,&nbsp;Katie Snape ,&nbsp;Stephen Morris","doi":"10.1016/j.ejmg.2024.104969","DOIUrl":"10.1016/j.ejmg.2024.104969","url":null,"abstract":"<div><h3>Background</h3><p>The South West Thames Centre for Genomics implemented a wider diagnostic Next Generation Sequencing (NGS) gene panel for eligible cancer patients undergoing diagnostic testing whilst restricting data analysis and reporting for BRCA1/BRCA2/PALB2/CHEK2 1100delC only as per contemporaneous guidelines. This study investigated the cost-utility of reanalyzing existing diagnostic grade extended panel data for truncating germline pathogenic variants (GPVs) in known moderate risk cancer susceptibility genes (CSGs) and performing follow-up genetic testing for first-degree relatives if patients have an identified CSG allele.</p></div><div><h3>Methods</h3><p>Reanalysis of existing NGS data was undertaken in 889 samples from cancer patients contemporaneously eligible through the NHS England National Genomic Test Directory (NGTD) codes R207 (ovarian) or R208 (breast) who had tested negative for <em>BRCA1/BRCA2/PALB2</em> and <em>CHEK2</em> 1100delC founder variant. We modeled the cost and health outcomes for comparisons between: 1. Extending reanalysis to <em>ATM</em> truncating GPVs (partial extended testing) versus historical genetic testing, and 2. Extending analysis to <em>ATM</em> truncating GPV/<em>BRIP1</em> truncating <em>GPV</em>/<em>CHEK2</em> truncating GPV excluding <em>CHEK2</em> 1100delC/<em>RAD51C</em> truncating GPV/<em>RAD51D</em> truncating GPV (full extended testing) versus historical genetic testing.</p></div><div><h3>Results</h3><p>For partial extended testing, the ICER compared with historical genetic testing was UK£49,671/QALY. For full extended testing, the ICER compared with historical genetic testing of historical genetic testing was UK£5716/QALY. The full extended testing remained cost-effective with a 30% increase in genetic testing cost.</p></div><div><h3>Conclusion</h3><p>Where existing NGS data for cancer susceptibility genes is stored to diagnostic standard in UK laboratories, this study suggests it is cost-effective to analyze, report and clinically manage patients and relatives by extended analysis to an 8-gene panel compared to the historical genetic testing.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"72 ","pages":"Article 104969"},"PeriodicalIF":1.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000612/pdfft?md5=50cb4a23057fdd510638f4a901c6c944&pid=1-s2.0-S1769721224000612-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167594","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}