RT Journal Article
T1 Identification of Clinical Variants beyond the Exome in Inborn Errors of Metabolism.
A1 Soriano-Sexto, Alejandro
A1 Gallego, Diana
A1 Leal, Fatima
A1 Castejon-Fernandez, Natalia
A1 Navarrete, Rosa
A1 Alcaide, Patricia
A1 Couce, Maria L
A1 Martin-Hernandez, Elena
A1 Quijada-Fraile, Pilar
A1 Peña-Quintana, Luis
A1 Yahyaoui, Raquel
A1 Correcher, Patricia
A1 Ugarte, Magdalena
A1 Rodriguez-Pombo, Pilar
A1 Perez, Belen
K1 Allelic expression imbalance
K1 Differential gene expression
K1 Inherited metabolic disorders
K1 Multi-omics
K1 Targeted transcriptomics
AB 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.
PB MDPI
YR 2022
FD 2022-10-25
LK http://hdl.handle.net/10668/21206
UL http://hdl.handle.net/10668/21206
LA en
NO Soriano-Sexto A, Gallego D, Leal F, Castejón-Fernández N, Navarrete R, Alcaide P, et al. Identification of Clinical Variants beyond the Exome in Inborn Errors of Metabolism. Int J Mol Sci. 2022 Oct 25;23(21):12850
DS RISalud
RD Apr 11, 2025