Identification of Clinical Variants beyond the Exome in Inborn Errors of Metabolism.
Int J Mol Sci
; 23(21)2022 Oct 25.
Article
em En
| MEDLINE
| ID: mdl-36361642
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença da Urina de Xarope de Bordo
/
Erros Inatos do Metabolismo
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
/
Newborn
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Espanha