{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T21:26:44Z","timestamp":1769635604264,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,15]],"date-time":"2022-10-15T00:00:00Z","timestamp":1665792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01310"],"award-info":[{"award-number":["PI19\/01310"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["2017:SGR 1428"],"award-info":[{"award-number":["2017:SGR 1428"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["SLT002\/16\/00174"],"award-info":[{"award-number":["SLT002\/16\/00174"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["01KU2016B"],"award-info":[{"award-number":["01KU2016B"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union","award":["PI19\/01310"],"award-info":[{"award-number":["PI19\/01310"]}]},{"name":"European Union","award":["2017:SGR 1428"],"award-info":[{"award-number":["2017:SGR 1428"]}]},{"name":"European Union","award":["SLT002\/16\/00174"],"award-info":[{"award-number":["SLT002\/16\/00174"]}]},{"name":"European Union","award":["01KU2016B"],"award-info":[{"award-number":["01KU2016B"]}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["PI19\/01310"],"award-info":[{"award-number":["PI19\/01310"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2017:SGR 1428"],"award-info":[{"award-number":["2017:SGR 1428"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["SLT002\/16\/00174"],"award-info":[{"award-number":["SLT002\/16\/00174"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["01KU2016B"],"award-info":[{"award-number":["01KU2016B"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CERCA Programme\/Generalitat de Catalunya and by the Departament de Salut, Generalitat de Catalunya","award":["PI19\/01310"],"award-info":[{"award-number":["PI19\/01310"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya and by the Departament de Salut, Generalitat de Catalunya","award":["2017:SGR 1428"],"award-info":[{"award-number":["2017:SGR 1428"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya and by the Departament de Salut, Generalitat de Catalunya","award":["SLT002\/16\/00174"],"award-info":[{"award-number":["SLT002\/16\/00174"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya and by the Departament de Salut, Generalitat de Catalunya","award":["01KU2016B"],"award-info":[{"award-number":["01KU2016B"]}]},{"name":"German Bundesministerium fur Bildung und Forschung (BMBF)","award":["PI19\/01310"],"award-info":[{"award-number":["PI19\/01310"]}]},{"name":"German Bundesministerium fur Bildung und Forschung (BMBF)","award":["2017:SGR 1428"],"award-info":[{"award-number":["2017:SGR 1428"]}]},{"name":"German Bundesministerium fur Bildung und Forschung (BMBF)","award":["SLT002\/16\/00174"],"award-info":[{"award-number":["SLT002\/16\/00174"]}]},{"name":"German Bundesministerium fur Bildung und Forschung (BMBF)","award":["01KU2016B"],"award-info":[{"award-number":["01KU2016B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peroxisomal biogenesis disorders (PBDs) are a heterogeneous group of genetic diseases. Multiple peroxisomal pathways are impaired, and very long chain fatty acids (VLCFA) are the first line biomarkers for the diagnosis. The clinical presentation of PBDs may range from severe, lethal multisystemic disorders to milder, late-onset disease. The vast majority of PBDs belong to Zellweger Spectrum Disordes (ZSDs) and represents a continuum of overlapping clinical symptoms, with Zellweger syndrome being the most severe and Heimler syndrome the less severe disease. Mild clinical conditions frequently present normal or slight biochemical alterations, making the diagnosis of these patients challenging. In the present study we used a combined WES and RNA-seq strategy to diagnose a patient presenting with retinal dystrophy as the main clinical symptom. Results showed the patient was compound heterozygous for mutations in PEX1. VLCFA were normal, but retrospective analysis of lysosphosphatidylcholines (LPC) containing C22:0\u2013C26:0 species was altered. This simple test could avoid the diagnostic odyssey of patients with mild phenotype, such as the individual described here, who was diagnosed very late in adult life. We provide functional data in cell line models that may explain the mild phenotype of the patient by demonstrating the hypomorphic nature of a deep intronic variant altering PEX1 mRNA processing.<\/jats:p>","DOI":"10.3390\/ijms232012367","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T02:29:46Z","timestamp":1665973786000},"page":"12367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Diagnostic Odyssey in an Adult Patient with Ophthalmologic Abnormalities and Hearing Loss: Contribution of RNA-Seq to the Diagnosis of a PEX1 Deficiency"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6863-3993","authenticated-orcid":false,"given":"Gerard","family":"Mu\u00f1oz-Pujol","sequence":"first","affiliation":[{"name":"Secci\u00f3 d\u2019Errors Cong\u00e8nits del Metabolisme-IBC, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic de Barcelona, IDIBAPS, CIBERER, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Socorro","family":"Alforja-Castiella","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine and Health Science, Universitat de Barcelona, Hospital Cl\u00ednic de Barcelona, 08028 Barcelon, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1812-9323","authenticated-orcid":false,"given":"Ricardo","family":"Casaroli-Marano","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine and Health Science, Universitat de Barcelona, Hospital Cl\u00ednic de Barcelona, 08028 Barcelon, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5120-4001","authenticated-orcid":false,"given":"Blai","family":"Morales-Romero","sequence":"additional","affiliation":[{"name":"Secci\u00f3 d\u2019Errors Cong\u00e8nits del Metabolisme-IBC, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic de Barcelona, IDIBAPS, CIBERER, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2132-4138","authenticated-orcid":false,"given":"Judit","family":"Garc\u00eda-Villoria","sequence":"additional","affiliation":[{"name":"Secci\u00f3 d\u2019Errors Cong\u00e8nits del Metabolisme-IBC, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic de Barcelona, IDIBAPS, CIBERER, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-3643","authenticated-orcid":false,"given":"Vicente A.","family":"Y\u00e9pez","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine, Technical University of Munich, 81675 Munich, Germany"},{"name":"Department of Informatics, Technical University of Munich, 85748 Garching, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8924-8365","authenticated-orcid":false,"given":"Julien","family":"Gagneur","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine, Technical University of Munich, 81675 Munich, Germany"},{"name":"Department of Informatics, Technical University of Munich, 85748 Garching, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjana","family":"Gusic","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine, Technical University of Munich, 81675 Munich, Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen, 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2379-6286","authenticated-orcid":false,"given":"Holger","family":"Prokisch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine, Technical University of Munich, 81675 Munich, Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen, 85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederic","family":"Tort","sequence":"additional","affiliation":[{"name":"Secci\u00f3 d\u2019Errors Cong\u00e8nits del Metabolisme-IBC, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic de Barcelona, IDIBAPS, CIBERER, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2249-246X","authenticated-orcid":false,"given":"Antonia","family":"Ribes","sequence":"additional","affiliation":[{"name":"Secci\u00f3 d\u2019Errors Cong\u00e8nits del Metabolisme-IBC, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular, Hospital Cl\u00ednic de Barcelona, IDIBAPS, CIBERER, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.bbamcr.2015.11.015","article-title":"Human disorders of peroxisome metabolism and biogenesis","volume":"1863","author":"Waterham","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","unstructured":"Scriver, C.R., Beaudet, A.L., Sly, W.S., and Valle, D. (2001). The Peroxisomal Biogenesis Disorder, The Metabolic & Molecular Bases of Inherited Disease, Mc Graw-Hill."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.bbamcr.2006.09.010","article-title":"Peroxisome biogenesis disorders","volume":"1763","author":"Steinberg","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s13023-015-0368-9","article-title":"Zellweger spectrum disorders: Clinical overview and management approach","volume":"10","author":"Klouwer","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ymgme.2015.12.009","article-title":"Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines","volume":"117","author":"Braverman","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/j.bbadis.2012.04.006","article-title":"Genetics and molecular basis of human peroxisome biogenesis disorders","volume":"1822","author":"Waterham","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/ddrr.1113","article-title":"Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives","volume":"17","author":"Braverman","year":"2013","journal-title":"Dev. Disabil. Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3389\/fphys.2014.00307","article-title":"Peroxisome biogenesis in mammalian cells","volume":"5","author":"Fujiki","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wanders, R.J.A., Baes, M., Ribeiro, D., Ferdinandusse, S., and Waterham, H.R. (2022). The physiological functions of human peroxisomes. Physiol. Rev., ahead of print.","DOI":"10.1152\/physrev.00051.2021"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1055\/s-0036-1582140","article-title":"Clinical and Biochemical Pitfalls in the Diagnosis of Peroxisomal Disorders","volume":"47","author":"Klouwer","year":"2016","journal-title":"Neuropediatrics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.mcp.2018.02.001","article-title":"Peroxisomal disorders: Improved laboratory diagnosis, new defects and the complicated route to treatment","volume":"40","author":"Wanders","year":"2018","journal-title":"Mol. Cell. Probes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ymgme.2021.09.007","article-title":"Diagnostic challenges and disease management in patients with a mild Zellweger spectrum disorder phenotype","volume":"134","author":"Enns","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-019-1243-x","article-title":"Expanding the clinical and genetic spectrum of Heimler syndrome","volume":"14","author":"Gao","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1038\/ejhg.2016.62","article-title":"Spectrum of PEX1 and PEX6 variants in Heimler syndrome","volume":"11","author":"Smith","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1007\/s00415-016-8167-3","article-title":"Expanding the spectrum of PEX10-related peroxisomal biogenesis disorders: Slowly progressive recessive ataxia","volume":"63","author":"Renaud","year":"2016","journal-title":"J. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100615","DOI":"10.1016\/j.ymgmr.2020.100615","article-title":"Mild form of Zellweger Spectrum Disorders (ZSD) due to variants in PEX1: Detailed clinical investigation in a 9-years-old female","volume":"24","author":"Barillari","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"jcs236943","DOI":"10.1242\/jcs.236943","article-title":"Recent insights into peroxisome biogenesis and associated diseases","volume":"133","author":"Fujiki","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1055\/s-0041-1741383","article-title":"How to Detect Isolated PEX10-Related Cerebellar Ataxia?","volume":"53","author":"Nava","year":"2022","journal-title":"Neuropediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10545-015-9880-2","article-title":"Zellweger spectrum disorders: Clinical manifestations in patients surviving into adulthood","volume":"39","author":"Berendse","year":"2016","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.ajhg.2015.08.011","article-title":"Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6","volume":"97","author":"Ratbi","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.ejmg.2016.09.004","article-title":"Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene","volume":"59","author":"Ratbi","year":"2016","journal-title":"Eur. J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/mgg3.312","article-title":"Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: Copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome","volume":"5","author":"Neuhaus","year":"2017","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/ajmg.c.31823","article-title":"The peroxisomal disorder spectrum and Heimler syndrome: Deep phenotyping and review of the literature","volume":"184","author":"Jani","year":"2020","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/ajmg.1320390214","article-title":"Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs","volume":"39","author":"Heimler","year":"1991","journal-title":"Am. J. Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E467","DOI":"10.1002\/humu.20932","article-title":"Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders","volume":"30","author":"Yik","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/humu.21388","article-title":"Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder","volume":"32","author":"Ebberink","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_27","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_28","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_29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nrd.2017.246","article-title":"Addressing challenges in the diagnosis and treatment of rare genetic diseases","volume":"17","author":"Boycott","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: Towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","author":"Stenson","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15824","DOI":"10.1038\/ncomms15824","article-title":"Genetic diagnosis of Mendelian disorders via RNA sequencing","volume":"8","author":"Kremer","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s41436-019-0672-1","article-title":"Diagnostic utility of transcriptome sequencing for rare Mendelian diseases","volume":"22","author":"Lee","year":"2020","journal-title":"Genet. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cll.2020.02.004","article-title":"The Clinical Application of RNA Sequencing in Genetic Diagnosis of Mendelian Disorders","volume":"40","author":"Stenton","year":"2020","journal-title":"Clin Lab Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13073-022-01019-9","article-title":"Clinical implementation of RNA sequencing for Mendelian disease diagnostics","volume":"14","author":"Gusic","year":"2022","journal-title":"Genome Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"165900","DOI":"10.1016\/j.bbadis.2020.165900","article-title":"Longitudinal study of Pex1-G844D NMRI mouse model: A robust pre-clinical model for mild Zellweger spectrum disorder. Biochimica et biophysica acta","volume":"1866","author":"Demaret","year":"2020","journal-title":"Mol. Basis Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s13287-015-0149-3","article-title":"Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities","volume":"6","author":"Wang","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/nrm3700","article-title":"Peroxisomes take shape","volume":"14","author":"Smith","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ymgmr.2016.10.006","article-title":"Diagnosis of a mild peroxisomal phenotype with next-generation sequencing","volume":"9","author":"Ventura","year":"2016","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s10545-017-0064-0","article-title":"Evaluation of C26:0-lysophosphatidylcholine and C26:0-carnitine as diagnostic markers for Zellweger spectrum disorders","volume":"40","author":"Klouwer","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"690","DOI":"10.3389\/fcell.2020.00690","article-title":"Comparison of the Diagnostic Performance of C26:0-Lysophosphatidylcholine and Very Long-Chain Fatty Acids Analysis for Peroxisomal Disorders","volume":"8","author":"Jaspers","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1002\/humu.23114","article-title":"From Wet-Lab to Variations: Concordance and Speed of Bioinformatics Pipelines for Whole Genome and Whole Exome Sequencing","volume":"37","author":"Laurie","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.ajhg.2018.10.025","article-title":"OUTRIDER: A Statistical Method for Detecting Aberrantly Expressed Genes in RNA Sequencing Data","volume":"103","author":"Brechtmann","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41467-020-20573-7","article-title":"Detection of aberrant splicing events in RNA-seq data using FRASER","volume":"12","author":"Mertes","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1038\/s41596-020-00462-5","article-title":"Detection of aberrant gene expression events in RNA sequencing data","volume":"16","author":"Mertes","year":"2021","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12367\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:54:56Z","timestamp":1760144096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,15]]},"references-count":44,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms232012367"],"URL":"https:\/\/doi.org\/10.3390\/ijms232012367","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,15]]}}}