Orphanet Journal of Rare Diseases最新文献

{"title":"Intelligence quotient scores among early-treated phenylketonuria patients: results from a systematic literature review.","authors":"Fiona O'Sullivan, Ioannis Tomazos, Francjan J van Spronsen, Shelagh M Szabo, Maanasa Venkataraman, Lavanya Huria, Neil Smith, Lachlan Molony, Kim Ingalls, Kathleen Somera-Molina, Rongrong Zhang, Cary O Harding","doi":"10.1186/s13023-025-03830-0","DOIUrl":"10.1186/s13023-025-03830-0","url":null,"abstract":"<p><strong>Background: </strong>Phenylketonuria (PKU) is a rare condition that causes the accumulation of phenylalanine; without prompt diagnosis and treatment following birth, severe neurologic and cognitive impairments occur. While dietary management can help reduce Phe levels, adherence is challenging and deficits in cognitive function often remain. The importance of the exact features of dietary management, treatment, and control at different time points with respect to eventual IQ scores has not been established. The objective of the present study was to review and describe published data on the impact of PKU on cognition as measured by IQ among PKU patients receiving early dietary management.</p><p><strong>Methods: </strong>A systematic literature review was conducted following PRISMA guidelines to examine IQ among patients with PKU. Instruments used to assess IQ included the Wechsler Intelligence Scale, Culture Fair Intelligence Test and Stanford Binet Test. Results were reported overall and by subgroups.</p><p><strong>Results: </strong>Twenty-five out of 28 identified studies could be included in the review. Lower IQ scores were generally observed among those with high phenylalanine levels, although variations in the study populations hinder the ability to make comparisons. Mean IQ scores among those with PKU were consistently lower compared to control groups. Even though all patients in this review received early treatment, those with poor dietary adherence and higher phenylalanine levels tended to show poorer cognitive ability.</p><p><strong>Conclusions: </strong>Cognition is affected in PKU, despite early and continuous dietary management. Treatments are needed that reduce phenylalanine levels so that the burden of neurocognitive impairment in PKU can be alleviated.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"314"},"PeriodicalIF":3.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of vascular complications in Ehlers-Danlos syndrome: a systematic review and meta-analysis.","authors":"Abdelaziz A Awad, Ambana Yappalparvi, Mahalaqua Nazli Khatib, Roopashree R, Mandeep Kaur, Manish Srivastava, Amit Barwal, G V Siva Prasad, Pranchal Rajput, Rukshar Syed, Gajendra Sharma, Anand Prasoon, Muhammed Shabil, Ankit Punia, Megha Jagga, Rachana Mehta, Sanjit Sah, Prakasini Satapathy, Abhay M Gaidhane, Edward Mawejje, Ganesh Bushi","doi":"10.1186/s13023-025-03854-6","DOIUrl":"10.1186/s13023-025-03854-6","url":null,"abstract":"<p><strong>Background: </strong>Ehlers-Danlos Syndrome (EDS) comprises connective tissue disorders associated with increased vascular complication risks. This meta-analysis assesses the prevalence of vascular complications in among patients with EDS.</p><p><strong>Methods: </strong>The review was conducted following PRISMA guidelines. A comprehensive literature search was conducted in PubMed, Embase, and Web of Science until November 2024. Observational studies reporting vascular complications in EDS were included. Data extraction included demographics, complication types, and study design, and quality assessment was evaluated using the modified Newcastle-Ottawa Scale (NOS). Random-effects models and I² statistics assessed heterogeneity, while Doi plots evaluated publication bias.</p><p><strong>Results: </strong>Of the 1,772 articles screened, 12 met the inclusion criteria, reporting various vascular complications in EDS. The overall pooled prevalence of vascular complications was 30.03% (95% CI: 15.00-51.07%). The prevalence for the vEDS subtype was 42.36% (95% CI: 12.63-78.88%), for unspecified EDS was 18.65% (95% CI: 5.38-48.03%), and for hEDS was 19.77% (95% CI: 15.09-25.16%). Sensitivity analyses confirmed the stability of the pooled prevalence estimates, and DOI plots indicated minimal publication bias.</p><p><strong>Conclusions: </strong>This review highlights the high risk of vascular complications in vEDS, with moderate involvement in other EDS subtypes. Regular vascular monitoring, especially in vEDS, is crucial for early detection and intervention. Standardized diagnostic protocols and further research into genetic factors are needed to improve management strategies.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"312"},"PeriodicalIF":3.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keratin-associated epidermolysis bullosa simplex: phenotypes and challenges in clinical trials - a narrative review and systematic update.","authors":"Verena Wally, Tobias Welponer, Hans-Peter Wiesinger, Anja Diem, Konstantin Thiel, Martin Geroldinger, Georg Zimmermann, Julia I Hummel, Sonja Dorfer, Josefina Piñón Hofbauer, Johann W Bauer, Martin Laimer","doi":"10.1186/s13023-025-03822-0","DOIUrl":"10.1186/s13023-025-03822-0","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical research on innovative therapies for the rare genodermatosis epidermolysis bullosa (EB) faces significant challenges, including small sample sizes, disease heterogeneity with intra- and inter-individual variability, limited understanding of pathogenic mechanisms and natural disease course, as well as the lack of patient-centred core outcomes. Moreover, existing tools and techniques to assess disease activity and dynamics are heterogeneous, inconsistent, and may fail to consider or inaccurately emphasize particularities of individual patients and distinct EB subtypes.</p><p><strong>Methods: </strong>In order to exemplify the differences between keratin-associated subtypes of EB simplex (k-EBS), we summarized respective clinical characteristics in a narrative way. In addition, we performed a systematic review of the literature published over the last 5 years, with the aim to give an overview on outcomes and their assessments used in these patient populations.</p><p><strong>Results: </strong>This review summarises the methodological scope, strengths and limitations of outcome assessments in clinical trials for the k-EBS, a group of inherited skin fragility diseases characterised by their distinct phenotype of epidermal blistering.</p><p><strong>Conclusions: </strong>By presenting an overview of the clinical spectrum of k-EBS, we identified key gaps in current assessment methodologies and propose alternative approaches to optimise the evaluation of skin blistering, with the aim of enhancing the accuracy, reliability, and patient-relevance of clinical outcomes.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"313"},"PeriodicalIF":3.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity spectrum of pegvaliase: A pharmacovigilance analysis using the FAERS database.","authors":"Luyao Xu, Kaili Mao, Songyang Zhong, Huayu Sun, Hongliang Zheng, Zhenling Fu","doi":"10.1186/s13023-025-03864-4","DOIUrl":"10.1186/s13023-025-03864-4","url":null,"abstract":"<p><strong>Objective: </strong>This research aimed to assess the safety of pegvaliase through analyzed the data from the FAERS database, thus providing a theoretical foundation for the rational and safe application of pegvaliase in clinical settings.</p><p><strong>Methods: </strong>Pegvaliase-associated adverse event reports were searched in FAERS database from the 2018 Q3 to 2023 Q2. These data were further mined through Four different algorithms, including ROR, PRR, BCPNN, and EBGM.</p><p><strong>Results: </strong>A total of 5,076 AEs reports were obtained from the FAERS database. At the PTs level, it was discovered that AE reports associated with pegvaliase as the primary suspect were connected to the 27 SOCs. Among these PTs, 83 signals in total were found, and each of them concurrently complied with the four algorithms. Further, we ranked PTs first for arthralgia in order of frequency and first for decreased amino acid levels in order of signal intensity. The median time to onset of adverse reactions was 15 days.</p><p><strong>Conclusion: </strong>We mined and analyzed the AE signals of pegvaliase based on the FAERS database, it turned out that they were generally consistent with the drug inserts and clinical trial results. However, potential new AE signals were revealed, providing a basis for the identification of adverse reactions in the clinical setting.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"315"},"PeriodicalIF":3.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caregiving burden among caregivers of people with myasthenia gravis.","authors":"Sarah Dewilde, Nafthali H Tollenaar, Pierre Boulanger, Annie Archer, Raquel Pardo, Elena Cortés-Vicente, Renato Mantegazza, Fiammetta Vanoli, Sophie Lehnerer, Marc Pawlitzki, Malgorzata Heinrich, Femke De Ruyck, Glenn Phillips, Sandra Paci","doi":"10.1186/s13023-025-03842-w","DOIUrl":"10.1186/s13023-025-03842-w","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Informal caregivers play an important role in the lives of people with Myasthenia gravis (MG). This study aims to assess the caregiver burden (CB) experienced by caregivers of MG patients.</p><p><strong>Methods: </strong>A cross-sectional study design collected patient and caregiver data in Germany, Italy, Spain, the UK, and France. The Zarit Burden Interview (ZBI-22), EQ-5D-5L and bolt-on questions, and PROMIS Global Health-10 were used to measure CB and overall health-related quality of life (HRQoL).</p><p><strong>Results: </strong>Caregivers (N = 69) reported a mean ZBI-22 score of 24.3, with 40.6% reporting no burden, 47.8% mild-to-moderate burden, 8.7% moderate-to-severe burden, and 2.9% severe burden. The most impacted ZBI-22 dimensions were \"losing control over one's life\", \"financial burden\" and \"relationships with relatives\". Based on a generic health-related quality of life scale (EQ-5D-5L plus bolt-on questions), the dimensions that were more frequently reported among MG caregivers to cause moderate-to-extreme problems were: tiredness (43%), self-confidence (32%), and anxiety/depression (28%). EQ-5D-5L utilities (values from -1 to 1, reflecting overall HRQoL) were negatively associated with higher ZBI-22 scores (little or no burden: 0.942, mild-to-moderate burden: 0.864, moderate-to-severe burden: 0.783, severe burden: 0.570). Regarding PROMIS-10 items, 48% of caregivers reported often/always being bothered by anxiety, depression, or irritation; 47% reported being not at all or little able to carry out daily activities; and 37% reported having (very) severe fatigue.</p><p><strong>Conclusion: </strong>Informal caregivers of MG patients experience a substantial burden, impacting their physical, emotional, and financial well-being. Findings highlight the need for tailored interventions to alleviate CB and enhance the caregivers' overall HRQoL.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"311"},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The difference of variation types between late-onset multiple acyl-CoA dehydrogenase deficiency patients carrying biallelic and single heterozygous variations in ETFDH: a systematic review and meta-analysis.","authors":"Huiqiu Zhang, Jing Ma, Menghan Su, Junsen Zhao, Weisong Duan, Juan Wang, Dan Liu, Junhong Guo, Xueli Chang, Wei Zhang, Rongjuan Zhao","doi":"10.1186/s13023-025-03845-7","DOIUrl":"10.1186/s13023-025-03845-7","url":null,"abstract":"<p><strong>Background: </strong>Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disease chiefly caused by mutations in ETFDH gene. Mutations in the ETFDH gene lead to abnormal structure, impaired function, and increased degradation of ETFDH protein. However, it is not known why approximately 10% of patients carry single heterozygous variants in ETFDH. We speculate that different variation types (e.g., null variants and missense variants) partially account for the phenomenon.</p><p><strong>Methods: </strong>In this study, six databases were searched up until December 01, 2024. Studies describing late-onset MADD patients carrying ETFDH variations were included. The analyses focused on the differences in variation types, computational pathogenicity scores of missense variants, and clinical characteristics between patients with biallelic and single heterozygous variations (biallelic group vs heterozygous group).</p><p><strong>Results: </strong>Of the initially screened 3638 studies, 30 met the inclusion criteria, including 498 late-onset MADD patients with biallelic variations and 62 with single heterozygous variations in ETFDH. The relative frequency of patients carrying null variants was lower in the biallelic group (21%, 95% CI [16%-27%]) than that in the heterozygous group (34%, 95% CI [23%-48%]) (P = 0.044). Missense variants in the heterozygous group had stronger pathogenicity than those in the biallelic group, as reflected by the computational prediction tools, SIFT, PolyPhen-2 and metaRNN (P < 0.05). Patients carrying biallelic variations had a younger onset age and a higher level of serum creatine kinase at diagnosis (P < 0.05).</p><p><strong>Conclusions: </strong>Late-onset MADD patients carrying single heterozygous variations in ETFDH gene have distinct variation profiles and clinical severity compared to those harboring biallelic variations, which highlights the complexity of this disease.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"310"},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blueprint for clinical N-of-1 strategies with off-label precision treatments in monogenic epilepsies.","authors":"Victoria M Defelippe, Eva H Brilstra, Willem M Otte, Ghislaine J M W van Thiel, Helen J Cross, Finbar O'Callaghan, Valentina De Giorgis, Emilio Perucca, Kees P J Braun, Floor E Jansen","doi":"10.1186/s13023-025-03750-z","DOIUrl":"10.1186/s13023-025-03750-z","url":null,"abstract":"<p><p>Precision treatments for monogenic epilepsies, i.e. treatments that can at least partially reverse the biochemical consequences of a pathogenic gene variant, have been gradually emerging over the years. To date, however, information on the efficacy of these treatments is mostly based on case-reports and retrospective studies. As a result, utilisation of precision treatments often lack consistency and a pre-defined outcome monitoring plan. N-of-1 strategies in clinical care are pre-defined, individually tailored, repeated challenge-withdrawal therapeutic trials designed to assess the value of a treatment of interest for an individual. Despite their potential to improve clinical decision-making, N-of-1 strategies have been hampered by limited guidance on their implementation and lack of consensus on oversight procedures. To improve treatment selection for rare monogenic epilepsies, the PINPOINT initiative (Precision Treatments In MoNogenic EPilepsies: Observational Registry And N-of-1 Trial Recommendations) was set up as a collaborative effort within the European Reference Network for Rare and Complex Epilepsies. PINPOINT aims to develop recommendations for the design of N-of-1 strategies with off-label precision treatments for monogenic epilepsies. Using available N-of-1 trial manuals, different components of N-of-1 design were tailored to the context of epilepsy and oversight procedures were outlined. These efforts resulted in this guidance document-or blueprint for N-of-1 strategies for monogenic epilepsies in clinical care. This blueprint defines the characteristics of treatments and patients that would be suitable for N-of-1 strategies. Key principles for outcome measure selection, period duration and statistical analysis are defined. Consideration is given to interim assessment rules, which establish whether proceeding onto an additional treatment cycle is likely to provide significant advantages. Procedures for ethical oversight are proposed. This blueprint for N-of-1 strategies can be used as a basis for master protocols to optimise individualised clinical care in a standardised and consistent manner. We are confident that this document will provide physicians with the building blocks needed to elevate precision treatments for rare monogenic epilepsies out of their current landscape of inadequate evidence.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"309"},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing pain in patients with Fabry disease: findings from a web-based cross-sectional survey in the US.","authors":"Eric Wallace, Dawn Laney, Ibrahim Warsi, Connie Baldwin, Jack Johnson, Joseph Kupferman, Pronabesh DasMahapatra, Nicole Lyn","doi":"10.1186/s13023-025-03812-2","DOIUrl":"10.1186/s13023-025-03812-2","url":null,"abstract":"<p><strong>Background: </strong>Fabry disease (FD) is a rare, progressive disorder caused by pathogenic variants of the GLA gene resulting in the accumulation of toxic metabolites. Pain is a hallmark of FD, and patients often present with heterogeneous pain profiles. This cross-sectional, web-based survey was conducted to characterize pain and pain crises in patients with FD in the United States and explore the effects of sex, disease phenotypes, and treatment on pain.</p><p><strong>Results: </strong>A total of 66 participants (mean ± standard deviation [SD] age: 44.0 ± 12.7 years; females: 59.1%) completed the survey. Participants reported experiencing pain in upper (34.8%) and lower (43.9%) extremities several times a day and abdominal pain (31.8%) a few times a week. Overall, participants reported the nature of their pain as triggered (upper extremities: 47.0%; abdomen: 51.5%) or sudden (lower extremities: 57.6%). Female participants reported experiencing pain in upper (46.2%) and lower (48.7%) extremities several times a day and described it as sudden or triggered (48.7%) in upper extremities and sudden (61.5%) in lower extremities. Pain crises were reported in the lower extremities (80.0%), followed by the upper extremities (66.7%) and the abdomen (51.1%), and were often characterized as burning, tingling, or stabbing. A higher proportion of female participants (84.6%) than that of male participants (73.7%) reported pain crises in lower extremities. The duration of pain crises varied from 30 min to several days for different subgroups depending on sex and FD phenotypes. Most participants (81.0%) reported symptom improvement after 12 months of FD-specific treatment. Participants reported improvement in neuropathic symptoms (burning in hands, 45.9%), with an overall mean (± SD) satisfaction score of 7.2 (± 1.7) with agalsidase beta as the most recent medication.</p><p><strong>Conclusions: </strong>Pain was largely reported to be triggered across all subgroups. Consistent pain profiles were noted in participants across sex and FD phenotypes. Female participants reported pain burden similar to that of male participants, and pain crisis experience was heterogeneous across the subgroups. Most participants reported improvement in symptoms after FD-specific treatment and a high treatment satisfaction score with agalsidase beta.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"308"},"PeriodicalIF":3.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal MRI radiomics in Beckwith-Wiedemann syndrome: a novel imaging approach for genotype identification.","authors":"Mei Bai, Xiansheng Wu, Jinghui Wang, Miaoying Zhang, Zhongwei Qiao, Lin Zhang, Jungang Liu","doi":"10.1186/s13023-025-03841-x","DOIUrl":"10.1186/s13023-025-03841-x","url":null,"abstract":"<p><strong>Purpose: </strong>To valuate the role of nonmalignant nephrological findings and renal MRI radiomics in differentiating molecular subtypes of Beckwith-Wiedemann syndrome (BWS).</p><p><strong>Materials and methods: </strong>Clinical data and abdominal MRI scans of 49 patients who underwent partial glossectomy between July 2019 and March 2024 were retrospectively analysed. Patients were categorized into two subtypes: BWS^UPD+IC1 (24 cases, with a predisposition to renal involvement) and BWS^IC2 (25 cases, with a lower risk of renal involvement), based on genetic testing. Pearson correlation analysis was conducted to evaluate the relationship between patients' age and renal volume. Radiomic features derived from the T2WI sequence and the ADC map were selected to construct single-sequence and combined models. Delong test was used to compare the performance of the models.</p><p><strong>Results: </strong>Clinically, the BWS^UPD+IC1 subtype exhibited a lower incidence of ear creases/pits (P = 0.048) and omphalocele/umbilical hernia (P = 0.032) compared to the BWS^IC2 subtype. Abdominal MRI findings indicated the BWS^UPD+IC1 subtype had larger total renal volume (P = 0.017) and a weaker correlation between total renal volume and patients' age (r = 0.38). Notably, 91.84% (45/49) of BWS patients exhibited a total renal volume exceeding the normal population's upper limit, with the IC1 subtype demonstrating the largest mean volume. The BWS^UPD+IC1 subtype showed higher incidences of nonmalignant renal (P = 0.013) and non-renal abdominal abnormalities. The T2WI, ADC, and combined models achieved the highest area under the receiver operating characteristic (ROC) curves (AUCs) of 0.837, 0.882 and 0.954 (P > 0.05), respectively.</p><p><strong>Conclusion: </strong>Nonmalignant renal abnormalities and MRI radiomics models have potential as alternative imaging tools for the identification of renal predisposition genotypes and the surveillance of renal size change in BWS patients.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"307"},"PeriodicalIF":3.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The m.3290T > C variant might be a protective factor against the pathogenic m.3243 A > G variant: a case study.","authors":"Ning Zhang, Zhikang Zhang, Ying Zhang, Xun Su, Yuzhou Gao, Jing Yang, Weiwei Zou, Yunxia Cao, Dongmei Ji","doi":"10.1186/s13023-025-03774-5","DOIUrl":"10.1186/s13023-025-03774-5","url":null,"abstract":"<p><p>The mitochondrial m.3243 A > G variant is a prevalent mitochondrial disease mutation that causes multisystem maternal inheritance disorders. While clinical severity typically correlates with mutation load, symptom manifestation may be influenced by other variants and environmental factors. Notably, the m.3290T > C variant has been hypothesized as a potential protective variant for m.3243 A > G pathogenicity, though clinical evidence remains limited. Here we reported a six-generation Chinese pedigree carrying both m.3243 A > G and homoplasmic m.3290T > C variants. Clinical and genetic analyses revealed that carriers with extremely high m.3243 A > G heteroplasmy (> 95%) exhibited severe symptoms, whereas those with moderate or high levels showed limited or no clinical symptoms. Our findings provide novel evidence for the protective role of m.3290T > C in mitigating m.3243 A > G pathogenicity, highlighting its potential clinical significance.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"306"},"PeriodicalIF":3.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}