Pub Date : 2026-01-01DOI: 10.1016/j.gim.2025.101628
Sonja A. Rasmussen, Ada Hamosh
{"title":"Response to Zlotogora","authors":"Sonja A. Rasmussen, Ada Hamosh","doi":"10.1016/j.gim.2025.101628","DOIUrl":"10.1016/j.gim.2025.101628","url":null,"abstract":"","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 1","pages":"Article 101628"},"PeriodicalIF":6.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.gim.2025.101666
Jessica Rosenblum, Ellen Rijckmans, Randy Osei, Katrien Janssens, Ligia Mateiu, Catharina Olsen, Katrien Stouffs, Marije Meuwissen, Anna C Jansen
Purpose: Transcriptomics by way of RNA sequencing (RNAseq) has emerged as a means to increase the diagnostic yield in genetic conditions. In this systematic review, we focus on the contribution of transcriptomics to improve the diagnostic yield in neurodevelopmental disorders.
Methods: We performed a systematic literature search in PubMed until January 2024, including articles describing diagnostic RNAseq on at least one individual with a primary neurodevelopmental phenotype. We extracted data on cohort size, phenotype, sample tissue, previously used diagnostic methods, added diagnostic yield of RNAseq, the use of control samples, and technical aspects of the RNA sequencing methodology.
Results: 17 articles were eligible for inclusion in the systematic review. We found an average added diagnostic yield of 15·5% through RNA sequencing for individuals with neurodevelopmental disorders. There is heterogeneity in the tissue type, reported quality measures, and the computational pipeline.
Conclusion: The significantly increased diagnostic yield demonstrates the value of this novel tool in the diagnostic setting of neurodevelopmental disorders. Our results offer an overview of common methodologies for RNAseq and allow us to formulate recommendations for genetic labs and clinicians when implementing RNAseq as a diagnostic tool. Lastly, we provide recommendations for future publications in order to increase transparency and reproducibility.
{"title":"RNA sequencing offers new diagnostic opportunities in neurodevelopmental disorders: a systematic review.","authors":"Jessica Rosenblum, Ellen Rijckmans, Randy Osei, Katrien Janssens, Ligia Mateiu, Catharina Olsen, Katrien Stouffs, Marije Meuwissen, Anna C Jansen","doi":"10.1016/j.gim.2025.101666","DOIUrl":"https://doi.org/10.1016/j.gim.2025.101666","url":null,"abstract":"<p><strong>Purpose: </strong>Transcriptomics by way of RNA sequencing (RNAseq) has emerged as a means to increase the diagnostic yield in genetic conditions. In this systematic review, we focus on the contribution of transcriptomics to improve the diagnostic yield in neurodevelopmental disorders.</p><p><strong>Methods: </strong>We performed a systematic literature search in PubMed until January 2024, including articles describing diagnostic RNAseq on at least one individual with a primary neurodevelopmental phenotype. We extracted data on cohort size, phenotype, sample tissue, previously used diagnostic methods, added diagnostic yield of RNAseq, the use of control samples, and technical aspects of the RNA sequencing methodology.</p><p><strong>Results: </strong>17 articles were eligible for inclusion in the systematic review. We found an average added diagnostic yield of 15·5% through RNA sequencing for individuals with neurodevelopmental disorders. There is heterogeneity in the tissue type, reported quality measures, and the computational pipeline.</p><p><strong>Conclusion: </strong>The significantly increased diagnostic yield demonstrates the value of this novel tool in the diagnostic setting of neurodevelopmental disorders. Our results offer an overview of common methodologies for RNAseq and allow us to formulate recommendations for genetic labs and clinicians when implementing RNAseq as a diagnostic tool. Lastly, we provide recommendations for future publications in order to increase transparency and reproducibility.</p>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":" ","pages":"101666"},"PeriodicalIF":6.2,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.gim.2025.101670
Anna Luiza Braga Albuquerque , Maria Inez Dacoregio , Cainã Gonçalves Rodrigues , Débora Romeo Bertola , Paulo Victor Zattar Ribeiro
Purpose
Achondroplasia is the most common skeletal dysplasia, caused by gain-of-function variants in FGFR3, resulting in constitutive receptor activation and downstream inhibition of endochondral ossification. In 2021, the first targeted therapy, vosoritide, was approved in some countries after a landmark randomized trial. Although findings are promising, evidence is limited to modest-sized cohorts. To address this, we conducted a systematic review and meta-analysis of available vosoritide data.
Methods
A systematic search of PubMed, Cochrane, and Embase was conducted. Data were extracted according to Cochrane guidelines. Outcomes consistently reported were synthesized using R (v4.5) to generate forest plots.
Results
Ten studies were analyzed, encompassing 696 pediatric patients. Meta-analysis of single means showed that height z-score variation after 12 months of treatment was 0.32 (95% CI 0.25-0.40), annualized growth rate was 1.82 cm/year higher after treatment (95% CI 1.46-2.18), and the ratio between sitting height and height showed −0.0089 decrease (95% CI −0.0157 to −0.0020). Studies reported uniform profiles of adverse events, mostly limited to mild injection-site related issues and no serious complications.
Conclusion
This meta-analysis shows that real-world observational data on vosoritide in children with achondroplasia replicate clinical trial findings, with greater gains in linear growth and a similarly favorable safety profile.
{"title":"Real-world outcomes of vosoritide in achondroplasia: A systematic review and meta-analysis of multinational clinical evidence","authors":"Anna Luiza Braga Albuquerque , Maria Inez Dacoregio , Cainã Gonçalves Rodrigues , Débora Romeo Bertola , Paulo Victor Zattar Ribeiro","doi":"10.1016/j.gim.2025.101670","DOIUrl":"10.1016/j.gim.2025.101670","url":null,"abstract":"<div><h3>Purpose</h3><div>Achondroplasia is the most common skeletal dysplasia, caused by gain-of-function variants in <em>FGFR3</em>, resulting in constitutive receptor activation and downstream inhibition of endochondral ossification. In 2021, the first targeted therapy, vosoritide, was approved in some countries after a landmark randomized trial. Although findings are promising, evidence is limited to modest-sized cohorts. To address this, we conducted a systematic review and meta-analysis of available vosoritide data.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, Cochrane, and Embase was conducted. Data were extracted according to Cochrane guidelines. Outcomes consistently reported were synthesized using R (v4.5) to generate forest plots.</div></div><div><h3>Results</h3><div>Ten studies were analyzed, encompassing 696 pediatric patients. Meta-analysis of single means showed that height <em>z</em>-score variation after 12 months of treatment was 0.32 (95% CI 0.25-0.40), annualized growth rate was 1.82 cm/year higher after treatment (95% CI 1.46-2.18), and the ratio between sitting height and height showed −0.0089 decrease (95% CI −0.0157 to −0.0020). Studies reported uniform profiles of adverse events, mostly limited to mild injection-site related issues and no serious complications.</div></div><div><h3>Conclusion</h3><div>This meta-analysis shows that real-world observational data on vosoritide in children with achondroplasia replicate clinical trial findings, with greater gains in linear growth and a similarly favorable safety profile.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"28 3","pages":"Article 101670"},"PeriodicalIF":6.2,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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