Whole genome sequencing as a first-tier diagnostic test for infants in neonatal intensive care units: A pilot study in Brazil.

Autor: Migliavacca MP; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Sobreira J; Diagnósticos da América S.A., DASA, São Paulo, Brazil.; Hospital Infantil Sabará, São Paulo, Brazil., Bermeo D; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Gomes M; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Alencar D; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Sussuchi L; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Souza CA; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Silva JS; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Kroll JE; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Burger M; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Guarischi-Sousa R; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Villela D; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Yamamoto GL; Diagnósticos da América S.A., DASA, São Paulo, Brazil.; Instituto da Criança, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, Brazil., Milanezi F; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Horigoshi N; Hospital Infantil Sabará, São Paulo, Brazil., Cesar RG; Hospital Infantil Sabará, São Paulo, Brazil., de Carvalho WB; Instituto da Criança, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, Brazil., Honjo RS; Instituto da Criança, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, Brazil., Bertola DR; Hospital Infantil Sabará, São Paulo, Brazil., Kim CA; Instituto da Criança, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, Brazil., de Souza L; Hospital das Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil., Procianoy RS; Hospital das Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil., Silveria RC; Hospital das Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil., Rosenberg C; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Giugliani R; Diagnósticos da América S.A., DASA, São Paulo, Brazil.; Hospital das Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil., Campana GA; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Scapulatempo-Neto C; Diagnósticos da América S.A., DASA, São Paulo, Brazil., Sobreira N; Diagnósticos da América S.A., DASA, São Paulo, Brazil.; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Jun; Vol. 194 (6), pp. e63544. Date of Electronic Publication: 2024 Jan 23.
DOI: 10.1002/ajmg.a.63544
Abstrakt: In this pilot study, we aimed to evaluate the feasibility of whole genome sequencing (WGS) as a first-tier diagnostic test for infants hospitalized in neonatal intensive care units in the Brazilian healthcare system. The cohort presented here results from a joint collaboration between private and public hospitals in Brazil considering the initiative of a clinical laboratory to provide timely diagnosis for critically ill infants. We performed trio (proband and parents) WGS in 21 infants suspected of a genetic disease with an urgent need for diagnosis to guide medical care. Overall, the primary indication for genetic testing was dysmorphic syndromes (n = 14, 67%) followed by inborn errors of metabolism (n = 6, 29%) and skeletal dysplasias (n = 1, 5%). The diagnostic yield in our cohort was 57% (12/21) based on cases that received a definitive or likely definitive diagnostic result from WGS analysis. A total of 16 pathogenic/likely pathogenic variants and 10 variants of unknown significance were detected, and in most cases inherited from an unaffected parent. In addition, the reported variants were of different types, but mainly missense (58%) and associated with autosomal diseases (19/26); only three were associated with X-linked diseases, detected in hemizygosity in the proband an inherited from an unaffected mother. Notably, we identified 10 novel variants, absent from public genomic databases, in our cohort. Considering the entire diagnostic process, the average turnaround time from enrollment to medical report in our study was 53 days. Our findings demonstrate the remarkable utility of WGS as a diagnostic tool, elevating the potential of transformative impact since it outperforms conventional genetic tests. Here, we address the main challenges associated with implementing WGS in the medical care system in Brazil, as well as discuss the potential benefits and limitations of WGS as a diagnostic tool in the neonatal care setting.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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