دورية أكاديمية
Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile.
| العنوان: | Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile. |
|---|---|
| المؤلفون: | Poli MC; Program for Immunogenetics and Translational Immunology, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile.; Hospital Dr. Roberto del Río, Santiago, Chile., Rebolledo-Jaramillo B; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Lagos C; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Orellana J; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Moreno G; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Martín LM; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.; Unidad de Gestión Clínica del Niño, Hospital Padre Hurtado, Santiago, Chile., Encina G; Biosoluciones UDD, Santiago, Chile., Böhme D; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.; Biosoluciones UDD, Santiago, Chile., Faundes V; Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile., Zavala MJ; Hospital Base de Valdivia, Valdivia, Chile., Hasbún T; Department of Dermatology, Facultad de Medicina Universidad del Desarrollo, Clínica Alemana de Santiago, Vitacura, Chile.; Department of Dermatology, Hospital Exequiel González Cortés, Vitacura, Chile., Fischer S; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Brito F; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Araya D; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., Lira M; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile., de la Cruz J; Program for Immunogenetics and Translational Immunology, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clinica Alemana Universidad del Desarrollo, Santiago, Chile., Astudillo C; Hospital Dr. Roberto del Río, Santiago, Chile., Lay-Son G; Division of Pediatrics, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile., Cares C; Genetics Unit, Hospital Dr Luis Calvo Mackenna, Santiago, Chile., Aracena M; Genetics Unit, Hospital Dr Luis Calvo Mackenna, Santiago, Chile., Martin ES; Hospital Dr Guillermo Grant Benavente, Concepcion, Chile., Coban-Akdemir Z; University of Texas Health Science Center at Houston, School of Public Health, Department of Epidemiology, Human Genetics and Environmental Sciences, Santiago, Chile.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Posey JE; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Lupski JR; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Repetto GM; Rare Diseases Program, Center for Genetics and Genomics, Institute of Science and Innovation in Medicine, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile. grepetto@udd.cl.; Unidad de Gestión Clínica del Niño, Hospital Padre Hurtado, Santiago, Chile. grepetto@udd.cl. |
| المصدر: | European journal of human genetics : EJHG [Eur J Hum Genet] 2024 Jan 04. Date of Electronic Publication: 2024 Jan 04. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9302235 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5438 (Electronic) Linking ISSN: 10184813 NLM ISO Abbreviation: Eur J Hum Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2003->: London : Nature Publishing Group Original Publication: Basel ; New York : Karger, [1992- |
| مستخلص: | Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the "diagnostic odyssey" for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international collaboration with Baylor College of Medicine, and the local development was structured as a hybrid model, where clinical and bioinformatics analysis were performed in-house and sequencing outsourced abroad, due to lack of high-throughput equipment in Chile. We describe the implementation process and findings of the first 103 patients. They had heterogeneous phenotypes, including congenital anomalies, intellectual disabilities and/or immune system dysfunction. Patients underwent clinical exome or research exome sequencing, as solo cases or with parents using a trio design. We identified pathogenic, likely pathogenic or variants of unknown significance in genes related to the patients´ phenotypes in 47 (45.6%) of them. Half were de novo informative variants, and half of the identified variants have not been previously reported in public databases. DECIPHERD ended the diagnostic odyssey for many participants. This hybrid strategy may be useful for settings of similarly limited genomic resources and lead to discoveries in understudied populations. (© 2024. The Author(s).) |
| التعليقات: | Comment in: Eur J Hum Genet. 2024 Feb 13;:. (PMID: 38351294) |
| References: | Nguengang Wakap S, Lambert DM, Olry A, Rodwell C, Gueydan C, Lanneau V, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020;28:165–73. (PMID: 10.1038/s41431-019-0508-031527858) World Bank. Population, Total and Low and Middle Income Countries. 2021. https://data.worldbank.org/indicator/SP.POP.TOTL?locations=XO&name_desc=false . Dharssi S, Wong-Rieger D, Harold M, Terry S. Review of 11 national policies for rare diseases in the context of key patient needs. Orphanet J Rare Dis. 2017;12:63. Mar 31. (PMID: 10.1186/s13023-017-0618-0283592785374691) Boycott KM, Rath A, Chong JX, Hartley T, Alkuraya FS, Baynam G, et al. International cooperation to enable the diagnosis of all rare genetic diseases. Am J Hum Genet. 2017;100:695–705. (PMID: 10.1016/j.ajhg.2017.04.003284758565420351) Malinowski J, Miller DT, Demmer L, Gannon J, Pereira EM, Schroeder MC, et al. Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability. Genet Med. 2020;22:986–1004. (PMID: 10.1038/s41436-020-0771-z322032277222126) Manickam K, McClain MR, Demmer LA, Biswas S, Kearney HM, Malinowski J, et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23:2029–37. (PMID: 10.1038/s41436-021-01242-634211152) Stark Z, Schofield D, Alam K, Wilson W, Mupfeki N, Macciocca I, et al. Prospective comparison of the cost-effectiveness of clinical whole-exome sequencing with that of usual care overwhelmingly supports early use and reimbursement. Genet Med. 2017;19:867–74. (PMID: 10.1038/gim.2016.22128125081) Stark Z, Schofield D, Martyn M, Rynehart L, Shrestha R, Alam K, et al. Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness. Genet Med. 2019;21:173–80. (PMID: 10.1038/s41436-018-0006-829765138) Tan TY, Dillon OJ, Stark Z, Schofield D, Alam K, Shrestha R, et al. Diagnostic impact and cost-effectiveness of whole-exome sequencing for ambulant children with suspected monogenic conditions. JAMA Pediatr. 2017;171:855–62. (PMID: 10.1001/jamapediatrics.2017.1755287596865710405) Wright CF, Campbell P, Eberhardt RY, Aitken S, Perrett D, Brent S, et al. Genomic diagnosis of rare pediatric disease in the United Kingdom and Ireland. N Engl J Med. 2023;388:1559–71. (PMID: 10.1056/NEJMoa2209046370436377614484) National Center for Biotechnology Information (NCBI). Clinical and research tests for exome - Genetic Testing Registry (GTR). 2023. https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=exome . Hamadeh N, Van Rompaey C, Metreu E, Eapen SG. New World Bank country classifications by income level: 2022–2023. 2022. https://blogs.worldbank.org/opendata/new-world-bank-country-classifications-income-level-2022-2023 . Taruscio D, Salvatore M, Lumaka A, Carta C, Cellai LL, Ferrari G, et al. Undiagnosed diseases: needs and opportunities in 20 countries participating in the Undiagnosed Diseases Network International. Front Public Health. 2023;11:1079601. (PMID: 10.3389/fpubh.2023.10796013693571910017550) World Health Organization. Accelerating access to genomics for global health Promotion, implementation, collaboration, and ethical, legal, and social issues. A report of the WHO Science Council. 2022;1–46. https://apps.who.int/iris/handle/10665/359560 . Adachi T, El-Hattab AW, Jain R, Crespo KAN, Lazo CIQ, Scarpa M, et al. Enhancing equitable access to rare disease diagnosis and treatment around the world: a review of evidence, policies, and challenges. Int J Environ Res Public Health. 2023;20:4732 http://www.ncbi.nlm.nih.gov/pubmed/36981643 . (PMID: 10.3390/ijerph200647323698164310049067) Encina G, Castillo-Laborde C, Lecaros JA, Dubois-Camacho K, Calderón JFJF, Aguilera X, et al. Rare diseases in Chile: challenges and recommendations in universal health coverage context. Orphanet J Rare Dis. 2019;14:289. (PMID: 10.1186/s13023-019-1261-8319318416958742) Patrinos G, Lopez-Correa C. Genomic medicine in emerging economies: genomics for every nation. United Kingdom: Academic Press Inc.; 2018. Köhler S, Vasilevsky NA, Engelstad M, Foster E, McMurry J, Aymé S, et al. The human phenotype ontology in 2017. Nucleic Acids Res. 2017;45:D865–76. (PMID: 10.1093/nar/gkw103927899602) Davis MW, Jorgensen EM. ApE, A plasmid editor: a freely available DNA manipulation and visualization program. Front Bioinform. 2022;2:818619. https://doi.org/10.3389/fbinf.2022.818619 . eCollection 2022. Özen S. Changing concepts in familial Mediterranean fever: is it possible to have an autosomal-recessive disease with only one mutation? Arthritis Rheum. 2009;60:1575–7. (PMID: 10.1002/art.2456519479854) Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42:377–81. (PMID: 10.1016/j.jbi.2008.08.010) Vujic M, Heyer CM, Ars E, Hopp K, Markoff A, Örndal C, et al. Incompletely penetrant PKD1 alleles mimic the renal manifestations of ARPKD. J Am Soc Nephrol. 2010;21:1097–102. (PMID: 10.1681/ASN.2009101070205585383152226) Powis Z, Farwell Hagman KD, Mroske C, McWalter K, Cohen JS, Colombo R, et al. Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance. Clin Genet. 2018;93:752–61. (PMID: 10.1111/cge.1313228881385) Szczałuba K, Brzezinska M, Kot J, Rydzanicz M, Walczak A, Stawiński P, et al. SETD5 loss-of-function mutation as a likely cause of a familial syndromic intellectual disability with variable phenotypic expression. Am J Med Genet A. 2016;170:2322–7. (PMID: 10.1002/ajmg.a.3783227375234) Liu P, Meng L, Normand EA, Xia F, Song X, Ghazi A, et al. Reanalysis of clinical exome sequencing data. N Engl J Med. 2019;380:2478–80. (PMID: 10.1056/NEJMc1812033312164056934160) Quaio CRDC, Moreira CM, Chung CH, Perazzio SF, Dutra AP, Kim CA. Exome sequencing of 500 Brazilian patients with rare diseases: what we have learned. Sao Paulo Med J. 2022;140:734–6. (PMID: 10.1590/1516-3180.2022.0076.r1.21072022361024629514873) Koile D, Cordoba M, de Sousa Serro M, Kauffman MA, Yankilevich P. GenIO: a phenotype-genotype analysis web server for clinical genomics of rare diseases. BMC Bioinform. 2018;19:25. (PMID: 10.1186/s12859-018-2027-3) Hu X, Li N, Xu Y, Li G, Yu T, Yao RE, et al. Proband-only medical exome sequencing as a cost-effective first-tier genetic diagnostic test for patients without prior molecular tests and clinical diagnosis in a developing country: the China experience. Genet Med. 2018;20:1045–53. (PMID: 10.1038/gim.2017.19529095814) Veltman JA, Brunner HG. De novo mutations in human genetic disease. Nat Rev Genet. 2012;13:565–75. (PMID: 10.1038/nrg324122805709) Mohiuddin M, Kooy RF, Pearson CE. De novo mutations, genetic mosaicism and human disease. Front Genet. 2022;13:983668. (PMID: 10.3389/fgene.2022.983668362261919550265) Rocha CS, Secolin R, Rodrigues MR, Carvalho BS, Lopes-Cendes I. The Brazilian initiative on precision medicine (BIPMed): fostering genomic data-sharing of underrepresented populations. NPJ Genom Med. 2020;5:42. (PMID: 10.1038/s41525-020-00149-6330830117532430) Peña-Chilet M, Roldán G, Perez-Florido J, Ortuño FM, Carmona R, Aquino V, et al. CSVS, a crowdsourcing database of the Spanish population genetic variability. Nucleic Acids Res. 2021;49:D1130–7. (PMID: 10.1093/nar/gkaa79432990755) Coban-Akdemir Z, Song X, Ceballos FC, Davut P, Karaca E, Bayram Y, et al. The impact of the Turkish (TK) population variome on the genomic architecture of rare disease traits. bioRxiv. 2023; https://doi.org/10.1101/2020.04.27.064824 . Sobreira NLM, Arachchi H, Buske OJ, Chong JX, Hutton B, Foreman J, et al. Matchmaker exchange. In: current protocols in human genetics. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 2017. 201. p. 9.31.1–9.31.15. Costain G, Walker S, Marano M, Veenma D, Snell M, Curtis M, et al. Genome sequencing as a diagnostic test in children with unexplained medical complexity. JAMA Netw Open. 2020;3:e2018109. (PMID: 10.1001/jamanetworkopen.2020.18109329602817509619) Deshwar AR, Yuki KE, Hou H, Liang Y, Khan T, Celik A, et al. Trio RNA sequencing in a cohort of medically complex children. Am J Hum Genet. 2023;110:895–900. (PMID: 10.1016/j.ajhg.2023.03.0063699008410183368) Frésard L, Montgomery SB. Diagnosing rare diseases after the exome. Cold Spring Harb Mol Case Stud. 2018;4:a003392. (PMID: 10.1101/mcs.a003392305593146318767) United Nations Group for Sustainable Development Goals. Leaving no one behind: equality and non-discrimination at the heart of sustainable development. 2016. https://unsceb.org/sites/default/files/imported_files/CEB equality framework-A4-web-rev3.pdf . |
| معلومات مُعتمدة: | UM1 HG006542 United States HG NHGRI NIH HHS; UM1 HG006542 United States HG NHGRI NIH HHS; UM1 HG006542 United States HG NHGRI NIH HHS |
| تواريخ الأحداث: | Date Created: 20240104 Latest Revision: 20240213 |
| رمز التحديث: | 20240214 |
| DOI: | 10.1038/s41431-023-01523-5 |
| PMID: | 38177409 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1476-5438 |
|---|---|
| DOI: | 10.1038/s41431-023-01523-5 |