NPJ Genomic Medicine最新文献

{"title":"Author Correction: Possible association of 16p11.2 copy number variation with altered lymphocyte and neutrophil counts.","authors":"Giuliana Giannuzzi, Nicolas Chatron, Katrin Mannik, Chiara Auwerx, Sylvain Pradervand, Gilles Willemin, Kendra Hoekzema, Xander Nuttle, Jacqueline Chrast, Marie C Sadler, Eleonora Porcu, Yann Herault, Bertrand Isidor, Brigitte Gilbert-Dussardier, Evan E Eichler, Zoltan Kutalik, Alexandre Reymond","doi":"10.1038/s41525-023-00354-z","DOIUrl":"https://doi.org/10.1038/s41525-023-00354-z","url":null,"abstract":"","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"9"},"PeriodicalIF":5.3,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516743","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":"Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina.","authors":"Patricio G Schlottmann,&nbsp;José D Luna,&nbsp;Natalia Labat,&nbsp;María Belén Yadarola,&nbsp;Silvina Bainttein,&nbsp;Evangelina Esposito,&nbsp;Agustina Ibañez,&nbsp;Evangelina Ivón Barbaro,&nbsp;Alejandro Álvarez Mendiara,&nbsp;Carolina P Picotti,&nbsp;Andrea Chirino Misisian,&nbsp;Luciana Andreussi,&nbsp;Julieta Gras,&nbsp;Luciana Capalbo,&nbsp;Mauro Visotto,&nbsp;José E Dipierri,&nbsp;Emilio Alcoba,&nbsp;Laura Fernández Gabrielli,&nbsp;Silvia Ávila,&nbsp;María Emilia Aucar,&nbsp;Daniel M Martin,&nbsp;Gerardo Juan Ormaechea,&nbsp;M Eugenia Inga,&nbsp;Aníbal A Francone,&nbsp;Martin Charles,&nbsp;Tamara Zompa,&nbsp;Pablo Javier Pérez,&nbsp;Vanesa Lotersztein,&nbsp;Pedro J Nuova,&nbsp;Ivana B Canonero,&nbsp;Omar A Mahroo,&nbsp;Michel Michaelides,&nbsp;Gavin Arno,&nbsp;Malena Daich Varela","doi":"10.1038/s41525-023-00352-1","DOIUrl":"https://doi.org/10.1038/s41525-023-00352-1","url":null,"abstract":"<p><p>This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"8"},"PeriodicalIF":5.3,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9886952","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":"An intronic variant in TBX4 in a single family with variable and severe pulmonary manifestations.","authors":"Frances O Flanagan, Alexander M Holtz, Sara O Vargas, Casie A Genetti, Klaus Schmitz-Abe, Alicia Casey, John C Kennedy, Benjamin A Raby, Mary P Mullen, Martha P Fishman, Pankaj B Agrawal","doi":"10.1038/s41525-023-00350-3","DOIUrl":"10.1038/s41525-023-00350-3","url":null,"abstract":"<p><p>A male infant presented at term with neonatal respiratory failure and pulmonary hypertension. His respiratory symptoms improved initially, but he exhibited a biphasic clinical course, re-presenting at 15 months of age with tachypnea, interstitial lung disease, and progressive pulmonary hypertension. We identified an intronic TBX4 gene variant in close proximity to the canonical donor splice site of exon 3 (hg 19; chr17:59543302; c.401 + 3 A > T), also carried by his father who had a typical TBX4-associated skeletal phenotype and mild pulmonary hypertension, and by his deceased sister who died shortly after birth of acinar dysplasia. Analysis of patient-derived cells demonstrated a significant reduction in TBX4 expression resulting from this intronic variant. Our study illustrates the variable expressivity in cardiopulmonary phenotype conferred by TBX4 mutation and the utility of genetic diagnostics in enabling accurate identification and classification of more subtly affected family members.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"7"},"PeriodicalIF":5.3,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299099","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":"PDGF gene expression and p53 alterations contribute to the biology of diffuse astrocytic gliomas.","authors":"Mehul Kumar,&nbsp;Mathieu Meode,&nbsp;Michael Blough,&nbsp;Gregory Cairncross,&nbsp;Pinaki Bose","doi":"10.1038/s41525-023-00351-2","DOIUrl":"https://doi.org/10.1038/s41525-023-00351-2","url":null,"abstract":"<p><p>Diffuse, histologically lower grade astrocytomas of adults (LGAs) are classified based on the mutational status of the isocitrate dehydrogenase (IDH) genes. While wild-type (WT) LGAs often evolve quickly to glioblastoma (GBM), mutant tumors typically follow an indolent course. To find possible effectors of these different behaviors, we compared their respective transcriptomes. Unlike mutant LGAs, platelet-derived growth factor (PDGF) signaling was significantly enriched in WT tumors, and PDGFA was the top overexpressed gene in the pathway. Moreover, methylation of the PDGFA and PDGFD promoters emerged as a possible mechanism for their low expression in mutant tumors. Copy number gain of chromosome 7 co-occurred with high expression of PDGFA in WT cases, and high expression of PDGFA was associated with aneuploidy, extracellular matrix (ECM)-related immunosuppressive features and poor prognosis. We also noted that high PDGFA expression in WT cases occurred irrespective of tumor grade and that multiple mechanisms of p53 pathway inactivation accompanied progression to GBM in PDGFA-overexpressing tumors. Conversely, TP53 point mutations were an early and constant feature of mutant LGAs. Our results suggest that members of the PDGF gene family, in concert with different p53 pathway alterations, underlie LGA behaviors.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"6"},"PeriodicalIF":5.3,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10788646","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":"Scalable, high quality, whole genome sequencing from archived, newborn, dried blood spots.","authors":"Yan Ding,&nbsp;Mallory Owen,&nbsp;Jennie Le,&nbsp;Sergey Batalov,&nbsp;Kevin Chau,&nbsp;Yong Hyun Kwon,&nbsp;Lucita Van Der Kraan,&nbsp;Zaira Bezares-Orin,&nbsp;Zhanyang Zhu,&nbsp;Narayanan Veeraraghavan,&nbsp;Shareef Nahas,&nbsp;Matthew Bainbridge,&nbsp;Joe Gleeson,&nbsp;Rebecca J Baer,&nbsp;Gretchen Bandoli,&nbsp;Christina Chambers,&nbsp;Stephen F Kingsmore","doi":"10.1038/s41525-023-00349-w","DOIUrl":"https://doi.org/10.1038/s41525-023-00349-w","url":null,"abstract":"<p><p>Universal newborn screening (NBS) is a highly successful public health intervention. Archived dried bloodspots (DBS) collected for NBS represent a rich resource for population genomic studies. To fully harness this resource in such studies, DBS must yield high-quality genomic DNA (gDNA) for whole genome sequencing (WGS). In this pilot study, we hypothesized that gDNA of sufficient quality and quantity for WGS could be extracted from archived DBS up to 20 years old without PCR (Polymerase Chain Reaction) amplification. We describe simple methods for gDNA extraction and WGS library preparation from several types of DBS. We tested these methods in DBS from 25 individuals who had previously undergone diagnostic, clinical WGS and 29 randomly selected DBS cards collected for NBS from the California State Biobank. While gDNA from DBS had significantly less yield than from EDTA blood from the same individuals, it was of sufficient quality and quantity for WGS without PCR. All samples DBS yielded WGS that met quality control metrics for high-confidence variant calling. Twenty-eight variants of various types that had been reported clinically in 19 samples were recapitulated in WGS from DBS. There were no significant effects of age or paper type on WGS quality. Archived DBS appear to be a suitable sample type for WGS in population genomic studies.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"5"},"PeriodicalIF":5.3,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738585","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":"Bi-allelic ATG4D variants are associated with a neurodevelopmental disorder characterized by speech and motor impairment.","authors":"Marie Morimoto, Vikas Bhambhani, Nour Gazzaz, Mariska Davids, Paalini Sathiyaseelan, Ellen F Macnamara, Jennifer Lange, Anna Lehman, Patricia M Zerfas, Jennifer L Murphy, Maria T Acosta, Camille Wang, Emily Alderman, Sara Reichert, Audrey Thurm, David R Adams, Wendy J Introne, Sharon M Gorski, Cornelius F Boerkoel, William A Gahl, Cynthia J Tifft, May Christine V Malicdan","doi":"10.1038/s41525-022-00343-8","DOIUrl":"10.1038/s41525-022-00343-8","url":null,"abstract":"<p><p>Autophagy regulates the degradation of damaged organelles and protein aggregates, and is critical for neuronal development, homeostasis, and maintenance, yet few neurodevelopmental disorders have been associated with pathogenic variants in genes encoding autophagy-related proteins. We report three individuals from two unrelated families with a neurodevelopmental disorder characterized by speech and motor impairment, and similar facial characteristics. Rare, conserved, bi-allelic variants were identified in ATG4D, encoding one of four ATG4 cysteine proteases important for autophagosome biogenesis, a hallmark of autophagy. Autophagosome biogenesis and induction of autophagy were intact in cells from affected individuals. However, studies evaluating the predominant substrate of ATG4D, GABARAPL1, demonstrated that three of the four ATG4D patient variants functionally impair ATG4D activity. GABARAPL1 is cleaved or \"primed\" by ATG4D and an in vitro GABARAPL1 priming assay revealed decreased priming activity for three of the four ATG4D variants. Furthermore, a rescue experiment performed in an ATG4 tetra knockout cell line, in which all four ATG4 isoforms were knocked out by gene editing, showed decreased GABARAPL1 priming activity for the two ATG4D missense variants located in the cysteine protease domain required for priming, suggesting that these variants impair the function of ATG4D. The clinical, bioinformatic, and functional data suggest that bi-allelic loss-of-function variants in ATG4D contribute to the pathogenesis of this syndromic neurodevelopmental disorder.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"4"},"PeriodicalIF":4.7,"publicationDate":"2023-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9918471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10699389","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":"Cross center single-cell RNA sequencing study of the immune microenvironment in rapid progressing multiple myeloma.","authors":"William Pilcher, Beena E Thomas, Swati S Bhasin, Reyka G Jayasinghe, Lijun Yao, Edgar Gonzalez-Kozlova, Surendra Dasari, Seunghee Kim-Schulze, Adeeb Rahman, Jonathan Patton, Mark Fiala, Giulia Cheloni, Taxiarchis Kourelis, Madhav V Dhodapkar, Ravi Vij, Shaadi Mehr, Mark Hamilton, Hearn Jay Cho, Daniel Auclair, David E Avigan, Shaji K Kumar, Sacha Gnjatic, Li Ding, Manoj Bhasin","doi":"10.1038/s41525-022-00340-x","DOIUrl":"10.1038/s41525-022-00340-x","url":null,"abstract":"<p><p>Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM's progression is facilitated by complex interactions with the surrounding bone marrow (BM) cells, forming a microenvironment that supports tumor growth and drug resistance. Understanding the immune microenvironment is key to identifying factors that promote rapid progression of MM. To accomplish this, we performed a multi-center single-cell RNA sequencing (scRNA-seq) study on 102,207 cells from 48 CD138^- BM samples collected at the time of disease diagnosis from 18 patients with either rapid progressing (progression-free survival (PFS) < 18 months) or non-progressing (PFS > 4 years) disease. Comparative analysis of data from three centers demonstrated similar transcriptome profiles and cell type distributions, indicating subtle technical variation in scRNA-seq, opening avenues for an expanded multicenter trial. Rapid progressors depicted significantly higher enrichment of GZMK⁺ and TIGIT⁺ exhausted CD8⁺ T-cells (P = 0.022) along with decreased expression of cytolytic markers (PRF1, GZMB, GNLY). We also observed a significantly higher enrichment of M2 tolerogenic macrophages in rapid progressors and activation of pro-proliferative signaling pathways, such as BAFF, CCL, and IL16. On the other hand, non-progressive patients depicted higher enrichment for immature B Cells (i.e., Pre/Pro B cells), with elevated expression for markers of B cell development (IGLL1, SOX4, DNTT). This multi-center study identifies the enrichment of various pro-tumorigenic cell populations and pathways in those with rapid progressing disease and further validates the robustness of scRNA-seq data generated at different study centers.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"3"},"PeriodicalIF":4.7,"publicationDate":"2023-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9360522","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":"Transcriptomic analyses of patient peripheral blood with hemoglobin depletion reveal glioblastoma biomarkers.","authors":"Dan Qi,&nbsp;Yiqun Geng,&nbsp;Jacob Cardenas,&nbsp;Jinghua Gu,&nbsp;S Stephen Yi,&nbsp;Jason H Huang,&nbsp;Ekokobe Fonkem,&nbsp;Erxi Wu","doi":"10.1038/s41525-022-00348-3","DOIUrl":"https://doi.org/10.1038/s41525-022-00348-3","url":null,"abstract":"<p><p>Peripheral blood is gaining prominence as a noninvasive alternative to tissue biopsy to develop biomarkers for glioblastoma (GBM); however, widely utilized blood-based biomarkers in clinical settings have not yet been identified due to the lack of a robust detection approach. Here, we describe the application of globin reduction in RNA sequencing of whole blood (i.e., WBGR) and perform transcriptomic analysis to identify GBM-associated transcriptomic changes. By using WBGR, we improved the detection sensitivity of informatic reads and identified differential gene expression in GBM blood. By analyzing tumor tissues, we identified transcriptomic traits of GBM blood. Further functional enrichment analyses retained the most changed genes in GBM. Subsequent validation elicited a 10-gene panel covering mRNA, long noncoding RNA, and microRNA (i.e., GBM-Dx panel) that has translational potential to aid in the early detection or clinical management of GBM. Here, we report an integrated approach, WBGR, with comprehensive analytic capacity for blood-based marker identification.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"2"},"PeriodicalIF":5.3,"publicationDate":"2023-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9877004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10153935","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":"Personalized matched targeted therapy in advanced pancreatic cancer: a pilot cohort analysis.","authors":"Justin Shaya, Shumei Kato, Jacob J Adashek, Hitendra Patel, Paul T Fanta, Gregory P Botta, Jason K Sicklick, Razelle Kurzrock","doi":"10.1038/s41525-022-00346-5","DOIUrl":"10.1038/s41525-022-00346-5","url":null,"abstract":"<p><p>Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/patient = 2.5 (median) (range, 1-4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078-0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12-1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = 0.008). No grade 3-4 toxicities occurred. The longest responder achieved partial remission (17.5 months) by co-targeting MEK and CDK4/6 alterations (chemotherapy-free). Therefore, genomically matched targeted agent combinations were active in these advanced pancreatic cancers. Larger prospective trials are warranted.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"8 1","pages":"1"},"PeriodicalIF":4.7,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10575770","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":"Diagnostic potential of the amniotic fluid cells transcriptome in deciphering mendelian disease: a proof-of-concept.","authors":"Mianne Lee,&nbsp;Anna K Y Kwong,&nbsp;Martin M C Chui,&nbsp;Jeffrey F T Chau,&nbsp;Christopher C Y Mak,&nbsp;Sandy L K Au,&nbsp;Hei Man Lo,&nbsp;Kelvin Y K Chan,&nbsp;Vicente A Yépez,&nbsp;Julien Gagneur,&nbsp;Anita S Y Kan,&nbsp;Brian H Y Chung","doi":"10.1038/s41525-022-00347-4","DOIUrl":"https://doi.org/10.1038/s41525-022-00347-4","url":null,"abstract":"<p><p>RNA sequencing (RNA-seq) is emerging in genetic diagnoses as it provides functional support for the interpretation of variants of uncertain significance. However, the use of amniotic fluid (AF) cells for RNA-seq has not yet been explored. Here, we examined the expression of clinically relevant genes in AF cells (n = 48) compared with whole blood and fibroblasts. The number of well-expressed genes in AF cells was comparable to that in fibroblasts and much higher than that in blood across different disease categories. We found AF cells RNA-seq feasible and beneficial in prenatal diagnosis (n = 4) as transcriptomic data elucidated the molecular consequence leading to the pathogenicity upgrade of variants in CHD7 and COL1A2 and revising the in silico prediction of a variant in MYRF. AF cells RNA-seq could become a reasonable choice for postnatal patients with advantages over fibroblasts and blood as it prevents invasive procedures.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"7 1","pages":"74"},"PeriodicalIF":5.3,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10446244","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}