{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:58:42Z","timestamp":1785279522531,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014555","name":"Foundation for Scientific and Technological Development in Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014555","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Rare diseases affect approximately 6%\u20137% of the Brazilian population, representing a significant public health challenge due to diagnostic delays and inequitable access to genomic services. This study evaluates a 5-year implementation of next-generation sequencing (NGS) at a Reference Service for Rare Diseases (RDRS) within the Brazilian Unified Health System (SUS), examining diagnostic performance and barriers to equitable access to genomic medicine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cohort of 385 patients with suspected genetic disorders underwent clinical or whole-exome sequencing (CES\/WES) between 2019 and 2024. Exome analyses were guided by standardized Human Phenotype Ontology (HPO)\u2013based phenotypic characterization, resulting in an overall diagnostic yield of 38.7% (149\/385 cases).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 249 variants were identified across 165 genes, including 75 variants not previously reported in medical literature or public databases. Actionable secondary findings were detected in 3.2% of cases, involving pathogenic variants in genes related to cardiac disease, cancer predisposition, and anesthesia risk, underscoring the preventive potential of genomic testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The implementation of NGS in the Brazilian public health system is feasible and highly impactful, yielding a 38.7% diagnostic rate that significantly reduces the diagnostic odyssey for rare disease patients. Success was heavily dependent on a multidisciplinary approach, standardized HPO-based phenotypic characterization, and close clinical-laboratory integration. The identification of 75 novel variants highlights the genetic complexity of Brazil\u2019s admixed population and the challenges of interpreting variants of uncertain significance (VUS) in underrepresented groups. Furthermore, the detection of actionable secondary findings demonstrates the broader preventive potential of genomic testing, underscoring the need for expanded local databases, genomic literacy among clinicians, and robust ethical frameworks for patient management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1850909","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:10:19Z","timestamp":1785276619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Five-year outcomes of next-generation sequencing implementation at a Brazilian public health system reference centre for rare diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"Natana Chaves","family":"Rabelo","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica Jos\u00e9 Carlos Cabral de Almeida & Centro de Refer\u00eancia para Doen\u00e7as Raras \u2013 Instituto Nacional de Sa\u00fade da Mulher, da Crian\u00e7a e do Adolescente Fernandes Figueira (IFF) - FIOCRUZ","place":["Rio de Janeiro, Brazil"]},{"name":"Unidade de Gen\u00e9tica Cl\u00ednica, Centro de Gen\u00e9tica M\u00e9dica Jos\u00e9 Carlos Cabral de Almeida & Servi\u00e7o de Refer\u00eancia para Doen\u00e7as Raras \u2013 Instituto Nacional de Sa\u00fade da Mulher, da Crian\u00e7a e do Adolescente Fernandes Figueira (IFF) - FIOCRUZ","place":["Rio de Janeiro, Brazil"]},{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica Jos\u00e9 Carlos Cabral de Almeida, Instituto Nacional de Doen\u00e7as Raras - INRaras (INCT)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eduarda","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular\/Medicina Gen\u00f4mica, Centro de Gen\u00e9tica M\u00e9dica Jos\u00e9 Carlos Cabral de Almeida & Centro de Refer\u00eancia para Doen\u00e7as Raras \u2013 Instituto Nacional de Sa\u00fade da Mulher, da Crian\u00e7a e do Adolescente Fernandes Figueira (IFF) - 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