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oai:repisalud.isciii.es:20.500.12105/188432024-09-21T18:16:47Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16963col_20.500.12105_16966

00925njm 22002777a 4500 dc Soriano-Sexto, Alejandro author Gallego, Diana author Leal, Fátima author Castejón-Fernández, Natalia author Navarrete, Rosa author Alcaide, Patricia author Couce, María L author Martín-Hernández, Elena author Quijada-Fraile, Pilar author Peña-Quintana, Luis author Yahyaoui, Raquel author Correcher, Patricia author Ugarte, Magdalena author Rodríguez-Pombo, Pilar author Pérez, Belén author 2022-10-25 Inborn errors of metabolism (IEM) constitute a huge group of rare diseases affecting 1 in every 1000 newborns. Next-generation sequencing has transformed the diagnosis of IEM, leading to its proposed use as a second-tier technology for confirming cases detected by clinical/biochemical studies or newborn screening. The diagnosis rate is, however, still not 100%. This paper reports the use of a personalized multi-omics (metabolomic, genomic and transcriptomic) pipeline plus functional genomics to aid in the genetic diagnosis of six unsolved cases, with a clinical and/or biochemical diagnosis of galactosemia, mucopolysaccharidosis type I (MPS I), maple syrup urine disease (MSUD), hyperphenylalaninemia (HPA), citrullinemia, or urea cycle deficiency. Eight novel variants in six genes were identified: six (four of them deep intronic) located in GALE, IDUA, PTS, ASS1 and OTC, all affecting the splicing process, and two located in the promoters of IDUA and PTS, thus affecting these genes' expression. All the new variants were subjected to functional analysis to verify their pathogenic effects. This work underscores how the combination of different omics technologies and functional analysis can solve elusive cases in clinical practice. 10.3390/ijms232112850 1422-0067 International journal of molecular sciences http://hdl.handle.net/10668/21206 36361642 http://hdl.handle.net/20.500.12105/18843 allelic expression imbalance differential gene expression inherited metabolic disorders multi-omics targeted transcriptomics Identification of Clinical Variants beyond the Exome in Inborn Errors of Metabolism.