American Journal of Medical Genetics Part C: Seminars in Medical Genetics最新文献

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Multiorgan manifestations of COL4A1 and COL4A2 variants and proposal for a clinical management protocol. COL4A1和COL4A2变体的多器官表现及临床管理方案建议。
IF 2.8 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-07-17 DOI: 10.1002/ajmg.c.32099
Simone Gasparini, Simona Balestrini, Luigi Francesco Saccaro, Giacomo Bacci, Giorgia Panichella, Martino Montomoli, Gaetano Cantalupo, Stefania Bigoni, Giorgia Mancano, Simona Pellacani, Vincenzo Leuzzi, Nila Volpi, Francesco Mari, Federico Melani, Mara Cavallin, Tiziana Pisano, Giulio Porcedda, Augusto Vaglio, Davide Mei, Carmen Barba, Elena Parrini, Renzo Guerrini
{"title":"Multiorgan manifestations of COL4A1 and COL4A2 variants and proposal for a clinical management protocol.","authors":"Simone Gasparini, Simona Balestrini, Luigi Francesco Saccaro, Giacomo Bacci, Giorgia Panichella, Martino Montomoli, Gaetano Cantalupo, Stefania Bigoni, Giorgia Mancano, Simona Pellacani, Vincenzo Leuzzi, Nila Volpi, Francesco Mari, Federico Melani, Mara Cavallin, Tiziana Pisano, Giulio Porcedda, Augusto Vaglio, Davide Mei, Carmen Barba, Elena Parrini, Renzo Guerrini","doi":"10.1002/ajmg.c.32099","DOIUrl":"https://doi.org/10.1002/ajmg.c.32099","url":null,"abstract":"<p><p>COL4A1/2 variants are associated with highly variable multiorgan manifestations. Depicting the whole clinical spectrum of COL4A1/2-related manifestations is challenging, and there is no consensus on management and preventative strategies. Based on a systematic review of current evidence on COL4A1/2-related disease, we developed a clinical questionnaire that we administered to 43 individuals from 23 distinct families carrying pathogenic variants. In this cohort, we extended ophthalmological and cardiological examinations to asymptomatic individuals and those with only limited or mild, often nonspecific, clinical signs commonly occurring in the general population (i.e., oligosymptomatic). The most frequent clinical findings emerging from both the literature review and the questionnaire included stroke (203/685, 29.6%), seizures or epilepsy (199/685, 29.0%), intellectual disability or developmental delay (168/685, 24.5%), porencephaly/schizencephaly (168/685, 24.5%), motor impairment (162/685, 23.6%), cataract (124/685, 18.1%), hematuria (63/685, 9.2%), and retinal arterial tortuosity (58/685, 8.5%). In oligosymptomatic and asymptomatic carriers, ophthalmological investigations detected retinal vascular tortuosity (5/13, 38.5%), dysgenesis of the anterior segment (4/13, 30.8%), and cataract (2/13, 15.4%), while cardiological investigations were unremarkable except for mild ascending aortic ectasia in 1/8 (12.5%). Our multimodal approach confirms highly variable penetrance and expressivity in COL4A1/2-related conditions, even at the intrafamilial level with neurological involvement being the most frequent and severe finding in both children and adults. We propose a protocol for prevention and management based on individualized risk estimation and periodic multiorgan evaluations.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32099"},"PeriodicalIF":2.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Practicalities (and real-life experiences) of dementia in adults with Down syndrome. 唐氏综合症成人痴呆症的实际情况(和真实经历)。
IF 2.8 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-07-05 DOI: 10.1002/ajmg.c.32098
Ayesha Harisinghani, Clorinda Cottrell, Karen Donelan, Alice D Lam, Margaret Pulsifer, Stephanie L Santoro
{"title":"Practicalities (and real-life experiences) of dementia in adults with Down syndrome.","authors":"Ayesha Harisinghani, Clorinda Cottrell, Karen Donelan, Alice D Lam, Margaret Pulsifer, Stephanie L Santoro","doi":"10.1002/ajmg.c.32098","DOIUrl":"https://doi.org/10.1002/ajmg.c.32098","url":null,"abstract":"<p><p>Adults with down syndrome (DS) have a lifetime dementia risk in excess of 95%, with a median age of onset of 55 years, due to trisomy 21. Co-occurring Alzheimer's disease (AD) has increased morbidity and mortality, and it is now recommended to screen for AD in all adults with DS beginning at 40 years of age. In this manuscript, we present two clinical cases of adults with DS who developed AD summarizing their medical histories, presenting symptoms, path to diagnosis and psychosocial aspects of care collected from retrospective chart review with caregiver consent. These two cases were chosen due to their complexity and interwoven nature of the medical and psychosocial aspects, and highlight the complexity and nuance of caring for patients with DS and AD.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32098"},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
On stillness. 关于静止
IF 2.8 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-06-28 DOI: 10.1002/ajmg.c.32096
Linda Z Rossetti
{"title":"On stillness.","authors":"Linda Z Rossetti","doi":"10.1002/ajmg.c.32096","DOIUrl":"https://doi.org/10.1002/ajmg.c.32096","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32096"},"PeriodicalIF":2.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Occurrence of mosaic Down syndrome and prevalence of co-occurring conditions in Medicaid enrolled adults, 2016-2019. 2016-2019 年参加医疗补助计划的成人中马赛克唐氏综合征的发生率和并发症的流行率。
IF 2.8 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-06-25 DOI: 10.1002/ajmg.c.32097
Eric Rubenstein, Salina Tewolde, Brian G Skotko, Amy Michals, Juan Fortea
{"title":"Occurrence of mosaic Down syndrome and prevalence of co-occurring conditions in Medicaid enrolled adults, 2016-2019.","authors":"Eric Rubenstein, Salina Tewolde, Brian G Skotko, Amy Michals, Juan Fortea","doi":"10.1002/ajmg.c.32097","DOIUrl":"https://doi.org/10.1002/ajmg.c.32097","url":null,"abstract":"<p><strong>Background: </strong>Mosaic Down syndrome is a triplication of chromosome 21 in some but not all cells. Little is known about the epidemiology of mosaic Down syndrome. We described prevalence of mosaic Down syndrome and the co-occurrence of common chronic conditions in 94,533 Medicaid enrolled adults with any Down syndrome enrolled from 2016 to 2019.</p><p><strong>Methods: </strong>We identified mosaic Down syndrome using the International Classification of Diseases and Related Health Problems, tenth edition code for mosaic Down syndrome and compared to those with nonmosaic Down syndrome codes. We identified chronic conditions using established algorithms and compared prevalence by mosaicism.</p><p><strong>Results: </strong>In total, 1966 (2.08%) had claims for mosaic Down syndrome. Mosaicism did not differ by sex or race/ethnicity with similar age distributions. Individuals with mosaicism were more likely to present with autism (13.9% vs. 9.6%) and attention deficit hyperactivity disorder (17.7% vs. 14.0%) compared to individuals without mosaicism. In total, 22.3% of those with mosaic Down syndrome and 21.5% of those without mosaicism had claims for Alzheimer's dementia (Prevalence difference: 0.8; 95% Confidence interval: -1.0, 2.8). The mosaic group had 1.19 times the hazard of Alzheimer's dementia compared to the nonmosaic group (95% CI: 1.0, 1.3).</p><p><strong>Discussion: </strong>Mosaicism may be associated with a higher susceptibility to certain neurodevelopmental and neurodegenerative conditions, including Alzheimer's dementia. Our findings challenge previous assumptions about its protective effects in Down syndrome. Further research is necessary to explore these associations in greater depth.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32097"},"PeriodicalIF":2.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A plot TWIST. 情节曲折。
IF 3.1 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-06-18 DOI: 10.1002/ajmg.c.32090
Sophia R Meyer, Tara L Wenger
{"title":"A plot TWIST.","authors":"Sophia R Meyer, Tara L Wenger","doi":"10.1002/ajmg.c.32090","DOIUrl":"https://doi.org/10.1002/ajmg.c.32090","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32090"},"PeriodicalIF":3.1,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype. 伴有智力障碍的眼睑下垂症与 Helsmoortel-Van Der Aa 综合征具有相同的表征和表型。
IF 3.1 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-06-17 DOI: 10.1002/ajmg.c.32089
Camilla Sarli, Liselot van der Laan, Jack Reilly, Slavica Trajkova, Diana Carli, Alfredo Brusco, Michael A Levy, Raissa Relator, Jennifer Kerkhof, Haley McConkey, Matthew L Tedder, Cindy Skinner, Mariëlle Alders, Peter Henneman, Raoul C M Hennekam, Claudia Ciaccio, Stefano D'Arrigo, Antonio Vitobello, Laurence Faivre, Sacha Weber, Aline Vincent-Devulder, Laurence Perrin, Alexia Bourgois, Toshiyuki Yamamoto, Kay Metcalfe, Marcella Zollino, Usha Kini, Daniela Oliveira, Sergio B Sousa, Denise Williams, Gerarda Cappuccio, Bekim Sadikovic, Nicola Brunetti-Pierri
{"title":"Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.","authors":"Camilla Sarli, Liselot van der Laan, Jack Reilly, Slavica Trajkova, Diana Carli, Alfredo Brusco, Michael A Levy, Raissa Relator, Jennifer Kerkhof, Haley McConkey, Matthew L Tedder, Cindy Skinner, Mariëlle Alders, Peter Henneman, Raoul C M Hennekam, Claudia Ciaccio, Stefano D'Arrigo, Antonio Vitobello, Laurence Faivre, Sacha Weber, Aline Vincent-Devulder, Laurence Perrin, Alexia Bourgois, Toshiyuki Yamamoto, Kay Metcalfe, Marcella Zollino, Usha Kini, Daniela Oliveira, Sergio B Sousa, Denise Williams, Gerarda Cappuccio, Bekim Sadikovic, Nicola Brunetti-Pierri","doi":"10.1002/ajmg.c.32089","DOIUrl":"https://doi.org/10.1002/ajmg.c.32089","url":null,"abstract":"<p><p>Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between ADNP and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype-specific episignature. A distinct episignature was shared by 15 individuals with BIS-causing SMARCA2 pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNP variants. This represents first evidence of a sensitive phenotype-specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene-specific episignatures.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32089"},"PeriodicalIF":3.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Simpson-Golabi-Behmel syndrome. 辛普森-戈拉比-贝梅尔综合征。
IF 3.1 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-05-20 DOI: 10.1002/ajmg.c.32088
Alessandro Vaisfeld, Giovanni Neri
{"title":"Simpson-Golabi-Behmel syndrome.","authors":"Alessandro Vaisfeld, Giovanni Neri","doi":"10.1002/ajmg.c.32088","DOIUrl":"https://doi.org/10.1002/ajmg.c.32088","url":null,"abstract":"<p><p>The Simpson-Golabi-Behmel syndrome (SGBS; OMIM 312870) is an overgrowth/multiple congenital anomalies/dysplasia condition, inherited as an X-linked semi-dominant trait, with variable expressivity in males and reduced penetrance and expressivity in females. The clinical spectrum is broad, ranging from mild manifestations in both males and females to multiple malformations and neonatal death in the more severely affected cases. An increased risk of neoplasia is reported, requiring periodical surveillance. Intellectual development is normal in most cases. SGBS is caused by a loss-of-function mutation of the GPC3 gene, either deletions or point mutations, distributed all over the gene. Notably, GPC3 deletion/point mutations are not found in a significant proportion of clinically diagnosed SGBS cases. The protein product GPC3 is a glypican functioning as a receptor for Hh at the cell surface, involved in the Hh-Ptc-Smo signaling pathway, a regulator of cellular growth.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32088"},"PeriodicalIF":3.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Domain-specific phenotypes in LINS1-related disorder-A Chinese family with the Q92X variant and literature review. LINS1相关障碍的领域特异性表型--一个具有Q92X变体的中国家庭及文献综述。
IF 3.1 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-04-02 DOI: 10.1002/ajmg.c.32085
Xu-Ying Li, Zhanjun Wang, Yanping Yang, Ruichai Lin, Chaodong Wang
{"title":"Domain-specific phenotypes in LINS1-related disorder-A Chinese family with the Q92X variant and literature review.","authors":"Xu-Ying Li, Zhanjun Wang, Yanping Yang, Ruichai Lin, Chaodong Wang","doi":"10.1002/ajmg.c.32085","DOIUrl":"https://doi.org/10.1002/ajmg.c.32085","url":null,"abstract":"<p><p>LINS1 is the human homolog of the Drosophila segment polarity gene that encodes an essential regulator of the wingless/Wnt signaling. By 2011, only seven pedigrees (16 patients) with eight causative variants in LINS1 gene have been reported. These cases mainly presented with infancy-/child-onset neurodevelopmental disorders, facial dysmorphia, and other clinical features, and a wide spectrum of clinically distinct phenotypes were also manifested. In our study, two brothers in a family were admitted and diagnosed with child-onset movement disorders, slight intellectual disability, psychological symptoms, eye problems, urinary and bowel dysfunction, mitral value prolapse, and Q-T prolongation. By exome sequencing, we identified a nonsense homozygous pathogenic variant (LINS1: c.274C > T (p.Q92X)), which had been reported in a case diagnosed with intellectual disability and psychiatric disorders (such as schizophrenia and anxiety). Compared with this case, the clinical features of our cases were distinct. In particular, our cases displayed unusual features of heart and blood system. Furthermore, the genotype-phenotype relationship analysis suggested that distinct phenotypes presented in cases carrying variants in different domains of the LINS1 gene. In conclusions, our findings suggest the high clinical variations in the LINS1 variants-related disorders. Moreover, the Q92X might be a recurrent variant in Hans of Southern China.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"e32085"},"PeriodicalIF":3.1,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cover Image, Volume 196, Number 1, March 2024 封面图片,第 196 卷,第 1 号,2024 年 3 月
IF 3.1 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-03-11 DOI: 10.1002/ajmg.c.32084
{"title":"Cover Image, Volume 196, Number 1, March 2024","authors":"","doi":"10.1002/ajmg.c.32084","DOIUrl":"https://doi.org/10.1002/ajmg.c.32084","url":null,"abstract":"<p><b>Cover legend: Photo credit: Andy Meredith, man with Down syndrome. Andy Meredith Photography,</b> https://andymeredith.com\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140104495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Table of Contents, Volume 196, Number 1, March 2024 目录,第 196 卷,第 1 号,2024 年 3 月
IF 3.1 3区 医学
American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2024-03-11 DOI: 10.1002/ajmg.c.32047
{"title":"Table of Contents, Volume 196, Number 1, March 2024","authors":"","doi":"10.1002/ajmg.c.32047","DOIUrl":"https://doi.org/10.1002/ajmg.c.32047","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140104466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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