RT Journal Article
T1 Value of genetic analysis for confirming inborn errors of metabolism detected through the Spanish neonatal screening program.
A1 Navarrete, Rosa
A1 Leal, Fatima
A1 Vega, Ana I
A1 Morais-Lopez, Ana
A1 Garcia-Silva, Maria Teresa
A1 Martin-Hernandez, Elena
A1 Quijada-Fraile, Pilar
A1 Bergua, Ana
A1 Vives, Inmaculada
A1 Garcia-Jimenez, Inmaculada
A1 Yahyaoui, Raquel
A1 Pedron-Giner, Consuelo
A1 Belanger-Quintana, Amaya
A1 Stanescu, Sinziana
A1 Cañedo, Elvira
A1 Garcia-Campos, Oscar
A1 Bueno-Delgado, Maria
A1 Delgado-Pecellin, Carmen
A1 Vitoria, Isidro
A1 Rausell, Maria Dolores
A1 Balmaseda, Elena
A1 Couce, Mari Luz
A1 Desviat, Lourdes R
A1 Merinero, Begoña
A1 Rodriguez-Pombo, Pilar
A1 Ugarte, Magdalena
A1 Perez-Cerda, Celia
A1 Perez, Belen
K1 Lipid Metabolism, Inborn Errors
K1 Metabolism, Inborn Errors
K1 Mutation
K1 Neonatal Screening
AB The present work describes the value of genetic analysis as a confirmatory measure following the detection of suspected inborn errors of metabolism in the Spanish newborn mass spectrometry screening program. One hundred and forty-one consecutive DNA samples were analyzed by next-generation sequencing using a customized exome sequencing panel. When required, the Illumina extended clinical exome panel was used, as was Sanger sequencing or transcriptional profiling. Biochemical tests were used to confirm the results of the genetic analysis. Using the customized panel, the metabolic disease suspected in 83 newborns (59%) was confirmed. In three further cases, two monoallelic variants were detected for two genes involved in the same biochemical pathway. In the remainder, either a single variant or no variant was identified. Given the persistent absence of biochemical alterations, carrier status was assigned in 39 cases. False positives were recorded for 11. In five cases in which the biochemical pattern was persistently altered, further genetic analysis allowed the detection of two variants affecting the function of BCAT2, ACSF3, and DNAJC12, as well as a second, deep intronic variant in ETFDH or PTS. The present results suggest that genetic analysis using extended next-generation sequencing panels can be used as a confirmatory test for suspected inborn errors of metabolism detected in newborn screening programs. Biochemical tests can be very helpful when a diagnosis is unclear. In summary, simultaneous genomic and metabolomic analyses can increase the number of inborn errors of metabolism that can be confirmed following suggestive newborn screening results.
PB Nature Publishing Group
YR 2019
FD 2019-01-09
LK http://hdl.handle.net/10668/13404
UL http://hdl.handle.net/10668/13404
LA en
NO Navarrete R, Leal F, Vega AI, Morais-López A, Garcia-Silva MT, Martín-Hernández E, et al. Value of genetic analysis for confirming inborn errors of metabolism detected through the Spanish neonatal screening program. Eur J Hum Genet. 2019 Apr;27(4):556-562
NO This work was funded in part by grant PI16/00573, B2017/BMD-3721, the Fundación Isabel Gemio and the Fundación La Caixa (LCF/PR/PR16/11110018), an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa, and the European Regional Development Fund.
DS RISalud
RD Jul 6, 2025