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@ARTICLE{Cheerie:283022,
      author       = {Cheerie, David and Lauffer, Marlen C and Newton, Logan and
                      Amburgey, Kimberly and Beijer, Danique and Haque, Bushra and
                      Kalish, Brian T and Meserve, Margaret M and Oh, Rachel Y and
                      Pan, Amy Y and Reuter, Miriam S and Szego, Michael J and
                      Szuto, Anna and Aartsma-Rus, Annemieke and Axford, Michelle
                      M and Deshwar, Ashish R and Dowling, James J and Marshall,
                      Christian R and Ivakine, Zhenya and Synofzik, Matthis and
                      Yu, Timothy W and Costain, Gregory},
      collaboration = {N={1 Collaborative}},
      othercontributors = {Taylor Tavares, Ana Lisa and Aartsma-Rus, Annemieke and
                          Verran, Aubrie Soucy and Kaiwar, Charu and Beijer, Danique
                          and Cheerie, David and Sherrill, Emma and Costain, Gregory
                          and Newton, Logan and Meserve, Margaret M and Lauffer,
                          Marlen C and Synofzik, Matthis and Nolen, Nicole and
                          Leonard, Stefanie and Sanders, Stephan J and Yu, Timothy W},
      title        = {{S}creening rare genetic diagnoses for amenability to
                      bespoke antisense oligonucleotide therapy development: {A}
                      retrospective cohort study.},
      journal      = {Genetics in medicine},
      volume       = {28},
      number       = {1},
      issn         = {1098-3600},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-01434},
      pages        = {101597},
      year         = {2025},
      abstract     = {To estimate the proportion of molecular genetic diagnoses
                      in a real-world, phenotypically heterogeneous patient cohort
                      that are amenable to antisense oligonucleotide (ASO)
                      treatment.We retrospectively applied the N=1 Collaborative's
                      Variant Assessments toward Eligibility for Antisense
                      Oligonucleotide Treatment guidelines to all diagnostic
                      variants found by clinical genome-wide sequencing at a
                      single pediatric hospital in 532 patients over a 6-year
                      period. Variants were classified as either 'eligible,'
                      'likely eligible,' 'unlikely eligible,' or 'not eligible' in
                      relation to the different ASO approaches, or 'unable to
                      assess.'In total, 25 unique variants across 26 patients
                      $(4.9\%$ of 532 patients) were eligible or likely eligible
                      for ASO treatment at a molecular genetic level, via
                      canonical exon skipping (4), splice correction (3), or
                      messenger RNA knockdown (19). Only 8 of these molecular
                      genetic diagnoses were made within a year of symptom onset.
                      After considering disease and delivery related factors, 11
                      diagnoses were still considered candidates for bespoke ASO
                      development.A meaningful proportion of genetic diagnoses
                      identified by genome-wide sequencing may be amenable to ASO
                      treatment. These results underscore the importance of timely
                      diagnosis, and the proactive identification and accelerated
                      functional testing of genetic variants amenable to ASO
                      treatments.},
      keywords     = {Antisense oligonucleotides (Other) / Experimental therapy
                      (Other) / Inborn genetic disease (Other) / Rare disease
                      (Other)},
      cin          = {AG Gasser},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41090344},
      doi          = {10.1016/j.gim.2025.101597},
      url          = {https://pub.dzne.de/record/283022},
}