{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:20:20Z","timestamp":1773393620145,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI19\/01155"],"award-info":[{"award-number":["PI19\/01155"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["B2017\/BMD3721"],"award-info":[{"award-number":["B2017\/BMD3721"]}]},{"DOI":"10.13039\/501100008433","name":"Consejer\u00eda de Educaci\u00f3n, Juventud y Deporte, Comunidad de Madrid","doi-asserted-by":"publisher","award":["PI19\/01155"],"award-info":[{"award-number":["PI19\/01155"]}],"id":[{"id":"10.13039\/501100008433","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008433","name":"Consejer\u00eda de Educaci\u00f3n, Juventud y Deporte, Comunidad de Madrid","doi-asserted-by":"publisher","award":["B2017\/BMD3721"],"award-info":[{"award-number":["B2017\/BMD3721"]}],"id":[{"id":"10.13039\/501100008433","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019 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.<\/jats:p>","DOI":"10.3390\/ijms232112850","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T22:00:27Z","timestamp":1666735227000},"page":"12850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identification of Clinical Variants beyond the Exome in Inborn Errors of Metabolism"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8294-7166","authenticated-orcid":false,"given":"Alejandro","family":"Soriano-Sexto","sequence":"first","affiliation":[{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares, Centro de Biolog\u00eda Molecular, Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IdiPAZ, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-7316","authenticated-orcid":false,"given":"Diana","family":"Gallego","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares, Centro de Biolog\u00eda Molecular, Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IdiPAZ, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1tima","family":"Leal","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares, Centro de Biolog\u00eda Molecular, Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IdiPAZ, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Castej\u00f3n-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares, Centro de Biolog\u00eda Molecular, Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IdiPAZ, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Navarrete","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares, Centro de Biolog\u00eda Molecular, Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IdiPAZ, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-2049","authenticated-orcid":false,"given":"Patricia","family":"Alcaide","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico de Enfermedades Moleculares, Centro de Biolog\u00eda Molecular, Departamento de Biolog\u00eda Molecular, Universidad Aut\u00f3noma de Madrid, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IdiPAZ, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-9905","authenticated-orcid":false,"given":"Mar\u00eda L.","family":"Couce","sequence":"additional","affiliation":[{"name":"Unit for the Diagnosis and Treatment of Congenital Metabolic Diseases, Clinical University Hospital of Santiago de Compostela, Health Research Institute of Santiago de Compostela, University of Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Mart\u00edn-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Mitocondriales-Metab\u00f3licas Hereditarias, Servicio de Pediatr\u00eda, Centro de Referencia Nacional (CSUR) y Europeo (MetabERN) para Enfermedades Metab\u00f3licas Hereditarias, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1026-4854","authenticated-orcid":false,"given":"Pilar","family":"Quijada-Fraile","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Mitocondriales-Metab\u00f3licas Hereditarias, Servicio de Pediatr\u00eda, Centro de Referencia Nacional (CSUR) y Europeo (MetabERN) para Enfermedades Metab\u00f3licas Hereditarias, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6052-5894","authenticated-orcid":false,"given":"Luis","family":"Pe\u00f1a-Quintana","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Unit, Complejo Hospitalario Universitario Insular Materno-Infantil (CHUIMI), Universidad de Las Palmas de Gran Canaria, Asociaci\u00f3n Canaria para La Investigaci\u00f3n Pedi\u00e1trica, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de la Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN) ISCIII, 35016 Gran Canaria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6789-1563","authenticated-orcid":false,"given":"Raquel","family":"Yahyaoui","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders and Newborn Screening, Institute of Biomedical Research in M\u00e1laga (IBIMA-Plafatorma BIONAND), IBIMA-RARE, 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(2021). Combined Genome, Transcriptome and Metabolome Analysis in the Diagnosis of Childhood Cerebellar Ataxia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062990"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/jlb\/lsx038","article-title":"The Known Unknown: The Challenges of Genetic Variants of Uncertain Significance in Clinical Practice","volume":"4","year":"2017","journal-title":"J. Law Biosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10545-010-9135-1","article-title":"Present and Future of Antisense Therapy for Splicing Modulation in Inherited Metabolic Disease","volume":"33","author":"Vilageliu","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.ajhg.2017.11.007","article-title":"Allelic Expression Imbalance Promoting a Mutant PEX6 Allele Causes Zellweger Spectrum Disorder","volume":"101","author":"Falkenberg","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s10549-018-4826-7","article-title":"Genetic Dissection of the BRCA2 Promoter and Transcriptional Impact of DNA Variants","volume":"171","author":"Infante","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41467-017-02306-5","article-title":"A PRDX1 Mutant Allele Causes a MMACHC Secondary Epimutation in CblC Patients","volume":"9","author":"Oussalah","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1038\/s41467-018-04540-x","article-title":"Identification of Rare de Novo Epigenetic Variations in Congenital Disorders","volume":"9","author":"Barbosa","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41586-020-2434-2","article-title":"Whole-Genome Sequencing of Patients with Rare Diseases in a National Health System","volume":"583","author":"Turro","year":"2020","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1056\/NEJMoa1806627","article-title":"Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS","volume":"380","author":"Richmond","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41525-018-0053-8","article-title":"Meta-Analysis of the Diagnostic and Clinical Utility of Genome and Exome Sequencing and Chromosomal Microarray in Children with Suspected Genetic Diseases","volume":"3","author":"Clark","year":"2018","journal-title":"NPJ Genom. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/ng.355","article-title":"Mutations in the Seed Region of Human MiR-96 Are Responsible for Nonsyndromic Progressive Hearing Loss","volume":"41","author":"Redshaw","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1212\/WNL.0000000000003819","article-title":"Mutations in Noncoding Regions of GJB1 Are a Major Cause of X-Linked CMT","volume":"88","author":"Tomaselli","year":"2017","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1002\/humu.23394","article-title":"Disease-causing Mutations in the Promoter and Enhancer of the Ornithine Transcarbamylase Gene","volume":"39","author":"Jang","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14292","DOI":"10.1038\/s41598-018-32565-1","article-title":"Identification of a Limb Enhancer That Is Removed by Pathogenic Deletions Downstream of the SHOX Gene","volume":"8","author":"Skuplik","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.ajhg.2020.09.002","article-title":"Structural Variants Create New Topological-Associated Domains and Ectopic Retinal Enhancer-Gene Contact in Dominant Retinitis Pigmentosa","volume":"107","author":"Fiorentino","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/humu.24248","article-title":"Upstream ORF Frameshift Variants in the PAX6 5\u02b9UTR Cause Congenital Aniridia","volume":"42","author":"Filatova","year":"2021","journal-title":"Hum. Mutat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/s41591-019-0457-8","article-title":"Identification of Rare-Disease Genes Using Blood Transcriptome Sequencing and Large Control Cohorts","volume":"25","author":"Smail","year":"2019","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s10545-017-0133-4","article-title":"\u201cTranscriptomics\u201d: Molecular Diagnosis of Inborn Errors of Metabolism via RNA-Sequencing","volume":"41","author":"Kremer","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1093\/brain\/aww221","article-title":"Advantages and Pitfalls of an Extended Gene Panel for Investigating Complex Neurometabolic Phenotypes","volume":"139","author":"Reid","year":"2016","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/0006-291X(91)91489-Y","article-title":"A 17-Bp Insertion and a Phe215\u2192Cys Missense Mutation in the Dihydrolipoyl Transacylase (E2) MRNA from a Thiamine-Responsive Maple Syrup Urine Disease Patient WG-34","volume":"174","author":"Fisher","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s100380050047","article-title":"Molecular Basis of Intermittent Maple Syrup Urine Disease: Novel Mutations in the E2 Gene of the Branched-Chain \u03b1-Keto Acid Dehydrogenase Complex","volume":"43","author":"Tsuruta","year":"1998","journal-title":"J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00439-009-0752-4","article-title":"Transposable Elements in Disease-Associated Cryptic Exons","volume":"127","author":"Vorechovsky","year":"2010","journal-title":"Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/jmedgenet-2015-103144","article-title":"The Clinical Application of Genome-Wide Sequencing for Monogenic Diseases in Canada: Position Statement of the Canadian College of Medical Geneticists","volume":"52","author":"Boycott","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"a003392","DOI":"10.1101\/mcs.a003392","article-title":"Diagnosing Rare Diseases after the Exome","volume":"4","author":"Montgomery","year":"2018","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1056\/NEJMra1711801","article-title":"Next-Generation Sequencing to Diagnose Suspected Genetic Disorders","volume":"379","author":"Adams","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrg.2017.116","article-title":"Paediatric Genomics: Diagnosing Rare Disease in Children","volume":"19","author":"Wright","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/jimd.12130","article-title":"The Diagnosis of Inborn Errors of Metabolism by an Integrative \u201cMulti-omics\u201d Approach: A Perspective Encompassing Genomics, Transcriptomics, and Proteomics","volume":"43","author":"Stenton","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/jimd.12507","article-title":"How to Proceed after \u201cNegative\u201d Exome: A Review on Genetic Diagnostics, Limitations, Challenges, and Emerging New Multiomics Techniques","volume":"45","author":"Wortmann","year":"2022","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.bbagrm.2011.12.001","article-title":"MRNA Export and the TREX Complex","volume":"1819","author":"Katahira","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Gene Regul. Mech."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3233\/JAD-140717","article-title":"A Mutation in the 5\u2019-UTR of GRN Gene Associated with Frontotemporal Lobar Degeneration: Phenotypic Variability and Possible Pathogenetic Mechanisms","volume":"42","author":"Puoti","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41431-018-0330-0","article-title":"Value of Genetic Analysis for Confirming Inborn Errors of Metabolism Detected through the Spanish Neonatal Screening Program","volume":"27","author":"Navarrete","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The Mutational Constraint Spectrum Quantified from Variation in 141,456 Humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: Improving Access to Variant Interpretations and Supporting Evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/humu.21438","article-title":"den LOVD v.2.0: The next Generation in Gene Variant Databases","volume":"32","author":"Fokkema","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The Human Genomic Variant Search Engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1093\/nar\/gkp215","article-title":"Human Splicing Finder: An Online Bioinformatics Tool to Predict Splicing Signals","volume":"37","author":"Desmet","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10048-011-0279-4","article-title":"Genotype\u2013Phenotype Correlations in Sepiapterin Reductase Deficiency. A Splicing Defect Accounts for a New Phenotypic Variant","volume":"12","author":"Arrabal","year":"2011","journal-title":"Neurogenetics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/12850\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:02:12Z","timestamp":1760144532000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/12850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,25]]},"references-count":38,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232112850"],"URL":"https:\/\/doi.org\/10.3390\/ijms232112850","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,25]]}}}