Orphanet Journal of Rare Diseases最新文献

{"title":"International expert opinion on the considerations for combining vosoritide and limb surgery: a modified delphi study","authors":"Silvio Boero, Julia Vodopiutz, Mohamad Maghnie, Josep M. de Bergua, Ignacio Ginebreda, Hiroshi Kitoh, Micha Langendörfer, Antonio Leiva-Gea, Jason Malone, Philip McClure, Gabriel T. Mindler, Dmitry Popkov, Robert Rodl, Pablo Rosselli, Fabio Verdoni, Viktor Vilenskii, Aaron J. Huser","doi":"10.1186/s13023-024-03236-4","DOIUrl":"https://doi.org/10.1186/s13023-024-03236-4","url":null,"abstract":"Achondroplasia is the most common form of skeletal disorder with disproportionate short stature. Vosoritide is the first disease-specific, precision pharmacotherapy to increase growth velocity in children with achondroplasia. Limb surgery is a standard approach to increase height and arm span, improve proportionality and functionality, as well as correcting deformities. The aim of this study was to gain expert opinion on the combined use of vosoritide and limb surgery in children and adolescents with achondroplasia. An international expert panel of 17 clinicians and orthopaedic surgeons was convened, and a modified Delphi process undertaken. The panel reviewed 120 statements for wording, removed any unnecessary statements, and added any that they felt were missing. There were 26 statements identified as facts that were not included in subsequent rounds of voting. A total of 97 statements were rated on a ten-point scale where 1 was ‘Completely disagree’ and 10 ‘Completely agree’. A score of ≥ 7 was identified as agreement, and ≤ 4 as disagreement. All experts who scored a statement ≤ 4 were invited to provide comments. There was 100% agreement with several statements including, “Achieve a target height, arm span or upper limb length to improve daily activities” (mean level of agreement [LoA] 9.47, range 8–10), the “Involvement of a multidisciplinary team in a specialist centre to follow up the patient” (mean LoA 9.67, range 7–10), “Planning a treatment strategy based on age and pubertal stage” (mean LoA 9.60, range 8–10), and “Identification of short- and long-term goals, based on individualised treatment planning” (mean LoA 9.27, range 7–10), among others. The sequence of a combined approach and potential impact on the physes caused disagreement, largely due to a lack of available data. It is clear from the range of responses that this modified Delphi process is only the beginning of new considerations, now that a medical therapy for achondroplasia is available. Until data on a combined treatment approach are available, sharing expert opinion is a vital way of providing support and guidance to the clinical community.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do we care? Reporting of genetic diagnoses in multidisciplinary intellectual disability care: a retrospective chart review","authors":"Annelieke R. Müller, Erik Boot, Stijn B. Notermans, Carlo Schuengel, Lidewij Henneman, Martina C. Cornel, Mieke M. van Haelst, Mariëlle Alders, Clara D. M. van Karnebeek, Bas Bijl, Frits A. Wijburg, Agnies M. van Eeghen","doi":"10.1186/s13023-024-03323-6","DOIUrl":"https://doi.org/10.1186/s13023-024-03323-6","url":null,"abstract":"Advances in understanding the etiology of intellectual disability (ID) has led to insights in potential (targeted) treatments and personalized care. Implications of ID on health are often complex and require a multidisciplinary approach. The aim was to investigate the reporting of genetic diagnoses in multidisciplinary ID care and to identify associated clinical and demographic factors. A retrospective chart review was performed on a randomly selected sample of individuals (n = 380) of a large ID care organization in the Netherlands. Data on genetic etiology, including genetic testing and diagnoses, and clinical and demographic characteristics were collected from files held by multidisciplinary team members. Reports on genetic etiology were available in 40% of the study sample (n = 151), with a genetic diagnosis recorded in 34% (n = 51), which is 13% of the total sample. In those with reported genetic diagnoses, this was reported in 90% of medical, 39% of psychodiagnostic, and 75% of professional caregivers’ files. Older age, mild ID, and the legal representative not being a family member were associated with less reported information on genetic etiology. This study revealed that genetic diagnoses were often not reported in ID care files. Recommendations were formulated to reduce delay in diagnosis, and enable personalized care for individuals with ID.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CFTR modulators response of S737F and T465N CFTR variants on patient-derived rectal organoids","authors":"Karina Kleinfelder, Paola Melotti, Anca Manuela Hristodor, Cristina Fevola, Giovanni Taccetti, Vito Terlizzi, Claudio Sorio","doi":"10.1186/s13023-024-03334-3","DOIUrl":"https://doi.org/10.1186/s13023-024-03334-3","url":null,"abstract":"Predictions based on patient-derived materials of CFTR modulators efficacy have been performed lately in patient-derived cells, extending FDA-approved drugs for CF patients harboring rare variants. Here we developed intestinal organoids from subjects carrying S737F- and T465N-CFTR in trans with null alleles to evaluate their functional impact on CFTR protein function and their restoration upon CFTR modulator treatment. The characterization of S737F-CFTR was performed in two subjects recently assessed in nasal epithelial cells but not in colonoids. Our functional analysis (Ussing chamber) confirmed that S737F-CFTR is a mild variant with residual function as investigated in colonoids of patients with S737F/Dele22-24 and S737F/W1282X genotypes. An increase of current upon Elexacaftor/Tezacaftor/Ivacaftor (ETI) treatment was recorded for the former genotype. T465N is a poorly characterized missense variant that strongly impacts CFTR function, as almost no CFTR-mediated anion secretion was registered for T465N/Q39X colonoids. ETI treatment substantially improved CFTR-mediated anion secretion and increased the rescue of mature CFTR expression compared to either untreated colonoids or to dual CFTR modulator therapies. Our study confirms the presence of a residual function of the S737F variant and its limited response to CFTR modulators while predicting for the first time the potential clinical benefit of Trikafta® for patients carrying the rare T465N variant.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence empowering rare diseases: a bibliometric perspective over the last two decades","authors":"Peiling Ou, Ru Wen, Linfeng Shi, Jian Wang, Chen Liu","doi":"10.1186/s13023-024-03352-1","DOIUrl":"https://doi.org/10.1186/s13023-024-03352-1","url":null,"abstract":"To conduct a comprehensive bibliometric analysis of the application of artificial intelligence (AI) in Rare diseases (RDs), with a focus on analyzing publication output, identifying leading contributors by country, assessing the extent of international collaboration, tracking the emergence of research hotspots, and detecting trends through keyword bursts. In this bibliometric study, we identified and retrieved publications on AI applications in RDs spanning 2003 to 2023 from the Web of Science (WoS). We conducted a global research landscape analysis and utilized CiteSpace to perform keyword clustering and burst detection in this field. A total of 1501 publications were included in this study. The evolution of AI applications in RDs progressed through three stages: the start-up period (2003–2010), the steady development period (2011–2018), and the accelerated growth period (2019–2023), reflecting this field’s increasing importance and impact at the time of the study. These studies originated from 85 countries, with the United States as the leading contributor. “Mutation”, “Diagnosis”, and “Management” were the top three keywords with high frequency. Keyword clustering analysis identified gene identification, effective management, and personalized treatment as three primary research areas of AI applications in RDs. Furthermore, the keyword burst detection indicated a growing interest in the areas of “biomarker”, “predictive model”, and “data mining”, highlighting their potential to shape future research directions. Over two decades, research on the AI applications in RDs has made remarkable progress and shown promising results in the development. Advancing international transboundary cooperation is essential moving forward. Utilizing AI will play a more crucial role across the spectrum of RDs management, encompassing rapid diagnosis, personalized treatment, drug development, data integration and sharing, and continuous monitoring and care.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and phenotypic landscapes of X-linked hereditary hearing loss in the Chinese population","authors":"Haifeng Feng, Shasha Huang, Ying Ma, Jinyuan Yang, Yijin Chen, Guojian Wang, Mingyu Han, Dongyang Kang, Xin Zhang, Pu Dai, Yongyi Yuan","doi":"10.1186/s13023-024-03338-z","DOIUrl":"https://doi.org/10.1186/s13023-024-03338-z","url":null,"abstract":"Hearing loss (HL) is the most common sensory birth deficit worldwide, with causative variants in more than 150 genes. However, the etiological contribution and clinical manifestations of X-linked inheritance in HL remain unclear within the Chinese HL population. In this study, we focused on X-linked hereditary HL and aimed to assess its contribution to hereditary HL and identify the genotype–phenotype relationship. We performed a molecular epidemiological investigation of X-linked hereditary HL based on next-generation sequencing and third-generation sequencing in 3646 unrelated patients with HL. We also discussed the clinical features associated with X-linked non-syndromic HL-related genes based on a review of the literature. We obtained a diagnostic rate of 52.72% (1922/3646) among our patients; the aggregate contribution of HL caused by genes on the X chromosome in this cohort was ~ 1.14% (22/1922), and POU3F4 variants caused ~ 59% (13/22) of these cases. We found that X-linked HL was congenital or began during childhood in all cases, with representative audiological profiles or typical cochlear malformations in certain genes. Genotypic and phenotypic analyses showed that causative variants in PRPS1 and AIFM1 were mainly of the missense type, suggesting that phenotypic variability was correlated with the different effects that the replaced residues exert on structure and function. Variations in SMPX causing truncation of the protein product were associated with DFNX4, which resulted in typical audiological profiles before and after the age of 10 years, whereas nontruncated proteins typically led to distal myopathy. No phenotypic differences were identified in patients carrying POU3F4 or COL4A6 variants. Our work constitutes a preliminary evaluation of the molecular contribution of X-linked genes in heritable HL (~ 1.14%). The 15 novel variants reported here expand the mutational spectrum of these genes. Analysis of the genotype–phenotype relationship is valuable for X-linked HL precise diagnostics and genetic counseling. Elucidation of the pathogenic mechanisms and audiological profiles of HL can also guide choices regarding treatment modalities.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering a novel SERPING1 pathogenic variant: insights into the aggregation of C1-INH in hereditary angioedema","authors":"Lingxi Jiang, Chao Dai, Suyang Duan, Tingting Wang, Chunbao Xie, Luhan Zhang, Zimeng Ye, Xiumei Ma, Yi Shi","doi":"10.1186/s13023-024-03306-7","DOIUrl":"https://doi.org/10.1186/s13023-024-03306-7","url":null,"abstract":"Hereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterized by recurrent edema and a potentially fatal risk. Despite its severity, there is a notable lack of effective methods for predicting and preventing HAE attacks. This study aims to thoroughly investigate the underlying pathological mechanisms of HAE and identify potential biomarkers that could aid in its prediction and prevention. In our investigation, we have discovered a novel pathogenic variant of the SERPING1 gene, specifically c.708T > G, in a Han family affected by HAE. Our observations indicate that this variant leads to an increase in the accumulation of C1-INH within the endoplasmic reticulum (ER), resulting in the upregulation of GRP75 protein expression. This cascade of events resulted in Ca2+ overload, disruption of mitochondrial structure and function, and eventually triggered apoptosis. Using siRNA to knock down GRP75 mitigates cellular calcium overload and mitochondrial damage induced by the SERPING1 mutation. Based on our findings, we propose that the detection of intracellular Ca2+ concentration could serve as a valuable biomarker for predicting acute attacks of HAE in patients. This discovery holds significant implications for the development of more targeted and effective strategies in the management of HAE.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world multidisciplinary outcomes of onasemnogene abeparvovec monotherapy in patients with spinal muscular atrophy type 1: experience of the French cohort in the first three years of treatment","authors":"Isabelle Desguerre, Rémi Barrois, Frédérique Audic, Christine Barnerias, Brigitte Chabrol, Jean Baptiste Davion, Julien Durigneux, Caroline Espil-Taris, Marta Gomez-Garcia de la Banda, Marine Guichard, Arnaud Isapof, Marie Christine Nougues, Vincent Laugel, Laure Le Goff, Sandra Mercier, Anne Pervillé, Christian Richelme, Marie Thibaud, Catherine Sarret, Cyril Schweitzer, Hervé Testard, Valérie Trommsdorff, Catherine Vanhulle, Ulrike Walther-Louvier, Cécilia Altuzarra, Mondher Chouchane, Juliette Ropars, Susana Quijano-Roy, Claude Cances","doi":"10.1186/s13023-024-03326-3","DOIUrl":"https://doi.org/10.1186/s13023-024-03326-3","url":null,"abstract":"Spinal muscular atrophy type 1 (SMA1) is the most severe and early form of SMA, a genetic disease with motor neuron degeneration. Onasemnogene abeparvovec gene transfer therapy (GT) has changed the natural history of SMA1, but real-world data are scarce. A French national expert committee identified 95 newly diagnosed treatment-naive SMA1 patients between June 2019 and June 2022. We prospectively report on children treated with GT as the first and only therapy who had more than one-year of follow-up. Forty-six SMA1 patients received GT. Twelve patients received other treatments. Patients with respiratory insufficiency were oriented toward palliative care after discussion with families. Twenty-nine of the treated patients with more than 12 months of follow-up were included in the follow-up analysis. Among them, 17 had 24 months of follow-up. The mean age at treatment was 7.5 (2.1–12.5) months. Twenty-two patients had two SMN2 copies, and seven had three copies. One infant died in the month following GT due to severe thrombotic microangiopathy, and another died due to respiratory distress. Among the 17 patients with 24 months of follow-up, 90% required spinal bracing (15/17), three patients required nocturnal noninvasive ventilation, and two needed gastrostomy. Concerning motor milestones at the 24-month follow-up, all patients held their head, 15/17 sat for 30 s unassisted, and 12/17 stood with aid. Motor scores (CHOPINTEND and HINE-2) and thoracic circumference significantly improved in all patients. Our study shows favorable motor outcomes and preserved respiratory and feeding functions in treatment-naive SMA1 infants treated by GT as the first and only therapy before respiratory and bulbar dysfunctions occurred. Nevertheless, almost all patients developed spinal deformities.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis of bone mineral density in adults with phenylketonuria","authors":"Júlio C. Rocha, Álvaro Hermida, Cheryl J. Jones, Yunchou Wu, Gillian E. Clague, Sarah Rose, Kaleigh B. Whitehall, Kirsten K. Ahring, André L. S. Pessoa, Cary O. Harding, Fran Rohr, Anita Inwood, Nicola Longo, Ania C. Muntau, Serap Sivri, François Maillot","doi":"10.1186/s13023-024-03223-9","DOIUrl":"https://doi.org/10.1186/s13023-024-03223-9","url":null,"abstract":"Lifelong management of phenylketonuria (PKU) centers on medical nutrition therapy, including dietary phenylalanine (Phe) restriction in addition to Phe-free or low-Phe medical foods/protein substitutes. Studies have reported low bone mineral density (BMD) in mixed-age PKU populations, possibly related to long-term Phe restriction. Therefore, a meta-analysis investigating BMD specifically in adults with PKU was conducted. Studies reporting BMD-related outcomes were identified from a systematic literature review evaluating somatic comorbidities experienced by adults with PKU on a Phe-restricted diet (searched February 1, 2022, updated November 1, 2023). Risk of study bias was assessed (Scottish Intercollegiate Guidelines Network checklists). The primary outcome of the meta-analysis was pooled mean BMD Z-scores of different bones. Secondary outcomes were the prevalence of low BMD Z-scores at pre-specified thresholds. Subgroup analyses of mean BMD Z-scores (decade of study publication, controlled versus uncontrolled blood Phe levels, gender) were conducted. BMD-related data from 4097 individuals across 10 studies rated as at least acceptable quality were included. Mean BMD Z-scores were statistically significantly lower compared with an age-matched control or reference (non-PKU) population, across bones, but still within the expected range for age (> -2.0): lumbar spine (seven studies, n = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies, n = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies, n = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies, n = 157), -0.61 (95% CI: -0.77, -0.45). The small number of observations in the subgroup analyses resulted in a high degree of uncertainty, limiting interpretation. Estimated prevalence of BMD Z-scores ≤ -2.0 was 8% (95% CI: 5%, 13%; four studies, n = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies, n = 144). Adults with PKU had lower BMD Z-scores than the reference (non-PKU) population but < 1 in 10 were below the expected range for age. The low number of studies prevents identification of which population characteristics are most impacting BMD. This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476).","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pareto-principle in rare disease education: assessing the representation of common rare diseases in medical education and coding systems","authors":"Alexandra Berger, Kai Lars Grimm, Richard Noll, Thomas OF Wagner","doi":"10.1186/s13023-024-03347-y","DOIUrl":"https://doi.org/10.1186/s13023-024-03347-y","url":null,"abstract":"The Pareto Principle asserts that a large portion of results can be achieved with a small amount of effort. Wakap et al. found that around 80% of individuals with rare diseases (RD) suffer from one of 149 specific rare diseases. A significant challenge in the RD domain is the lack of information, compounded by the fact that most RD are not specifically codifiable in the ICD-10, leading to a deficit in reliable epidemiological data. Additionally, time constraints in medical education hinder the comprehensive teaching of all RD, contributing to the diagnostic odyssey problem through failure of recognizing diseases. We identified the most and second most prevalent RD (prevalences of 1–5/10,000 and 1–9/100,000, respectively) from the Orphanet Epidemiology File, totaling 454 diseases. We investigated the feasibility of specific coding using ICD-10-GM and whether these diseases were explicitly listed in the subject catalog (GK) of the second state examination in human medicine in Germany. A two-sided chi-square test was employed to identify statistically significant differences between prevalence groups. Out of 454 diseases, a total of 34% could be specifically coded in ICD-10-GM, with 49% of diseases in the 1–5/10,000 prevalence range (153 RD) and 26% in the 1–9/100,000 range (301 RD) having specific codes. Approximately 15% of all investigated diseases were part of the GK, with 25% of the most prevalent and 10% of the second most prevalent RD group, respectively. Statistically significant differences were observed between prevalence groups concerning the presence of a specific ICD-10-GM code and inclusion in the GK. Only 49% of the most prevalent RD can be specifically coded, highlighting the challenge of limited epidemiological data on RD. In Germany, the Alpha-ID was introduced in addition to ICD-10 in the inpatient setting to obtain more valid epidemiological data on RD. Recognizing the Pareto Principle’s applicability, the study emphasizes the importance of including the most common rare diseases in medical education. While recognizing the limitations, especially in covering ultra-rare diseases, the study underscores the potential benefits of enhancing medical curricula to improve rare disease awareness and diagnostic accuracy.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating carrier rates and prevalence of porphyria-associated gene variants in the Chinese population based on genetic databases","authors":"Yinan Wang, Nuoya Li, Songyun Zhang","doi":"10.1186/s13023-024-03287-7","DOIUrl":"https://doi.org/10.1186/s13023-024-03287-7","url":null,"abstract":"Porphyria is a group of rare metabolic disorders caused by mutations in the genes encoding crucial enzymes in the heme biosynthetic pathway. However, the lack of comprehensive genetic analysis of porphyria patients in the Chinese population makes identifying and diagnosing carriers of the condition challenging. Using the ChinaMAP database, we determined the frequencies of P/LP porphyria-associated gene variants according to the ACMG guidelines. We also calculated the carrier rates and prevalence of each type of porphyria in the Chinese population under Hardy–Weinberg equilibrium. Compared with the variants in the gnomAD database, the genetic spectrum of porphyria-related P/LP variants in the Chinese population is distinct. In the ChinaMAP database, we identified 23 variants. We estimated the carrier rates for autosomal dominant porphyrias (AIP, HCP, VP, PCT) in the Chinese population to be 1/1059, 1/1513, 1/10588, and 1/1765, respectively. For autosomal recessive porphyrias (ADP, EPP, HEP, CEP), the estimated carrier rates were 1/5294, 1/2117, 1/1765, and 1/2647, respectively, with predicted prevalence rates of 8.92 × 10−9, 7.51 × 10−5, 8.02 × 10−8, and 3.57 × 10−8, respectively. Notably, 12 of the variants we identified were unique to the Chinese population. The predicted prevalence rate of EPP was the highest among the various types of porphyria in the Chinese population, while the others were moderate to low. This is the first comprehensive genetic study on porphyria in the Chinese population. Clarifying the genetic characteristics of various porphyria types among the Chinese population provides scientifically sound reference data for both research and genetic screening to identify porphyria carriers.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}