{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:54:44Z","timestamp":1785437684236,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CERCA Programme\/Generalitat de Catalunya and Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca from the Autonomous Catalan Government","award":["2021 SGR 01492"],"award-info":[{"award-number":["2021 SGR 01492"]}]},{"name":"CERCA Programme\/Generalitat de Catalunya and Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca from the Autonomous Catalan Government","award":["AP171442019"],"award-info":[{"award-number":["AP171442019"]}]},{"name":"Fundaci\u00f3n M\u00fatua Madrile\u00f1a","award":["2021 SGR 01492"],"award-info":[{"award-number":["2021 SGR 01492"]}]},{"name":"Fundaci\u00f3n M\u00fatua Madrile\u00f1a","award":["AP171442019"],"award-info":[{"award-number":["AP171442019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Neurological disorders (ND) are diseases that affect the brain and the central and autonomic nervous systems, such as neurodevelopmental disorders, cerebellar ataxias, Parkinson\u2019s disease, or epilepsies. Nowadays, recommendations of the American College of Medical Genetics and Genomics strongly recommend applying next generation sequencing (NGS) as a first-line test in patients with these disorders. Whole exome sequencing (WES) is widely regarded as the current technology of choice for diagnosing monogenic ND. The introduction of NGS allows for rapid and inexpensive large-scale genomic analysis and has led to enormous progress in deciphering monogenic forms of various genetic diseases. The simultaneous analysis of several potentially mutated genes improves the diagnostic process, making it faster and more efficient. The main aim of this report is to discuss the impact and advantages of the implementation of WES into the clinical diagnosis and management of ND. Therefore, we have performed a retrospective evaluation of WES application in 209 cases referred to the Department of Biochemistry and Molecular Genetics of the Hospital Clinic of Barcelona for WES sequencing derived from neurologists or clinical geneticists. In addition, we have further discussed some important facts regarding classification criteria for pathogenicity of rare variants, variants of unknown significance, deleterious variants, different clinical phenotypes, or frequency of actionable secondary findings. Different studies have shown that WES implementation establish diagnostic rate around 32% in ND and the continuous molecular diagnosis is essential to solve the remaining cases.<\/jats:p>","DOI":"10.3390\/genes14040813","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T04:37:15Z","timestamp":1679978235000},"page":"813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-8915","authenticated-orcid":false,"given":"Mar\u00eda Isabel","family":"Alvarez-Mora","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer), 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-3929","authenticated-orcid":false,"given":"Laia","family":"Rodr\u00edguez-Revenga","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer), 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meritxell","family":"Jodar","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer), 08036 Barcelona, Spain"},{"name":"Molecular Biology of Reproduction and Development Research Group, Department of Biomedical Sciences, Faculty of Medicine, Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2766-0765","authenticated-orcid":false,"given":"Miriam","family":"Potrony","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer), 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer), 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Badenas","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer), 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Oriola","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7445-1267","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Villanueva-Ca\u00f1as","sequence":"additional","affiliation":[{"name":"Molecular Biology CORE (CDB), Hospital Cl\u00ednic de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, IDIBAPS, CIBERNED (CB06\/05\/0018-ISCIII), ERN-RND, Institut Cl\u00ednic de Neuroci\u00e8ncies UBNeuro (Maria de Maeztu Excellence Centre), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Valldeoriola","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, IDIBAPS, CIBERNED (CB06\/05\/0018-ISCIII), ERN-RND, Institut Cl\u00ednic de Neuroci\u00e8ncies UBNeuro (Maria de Maeztu Excellence Centre), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"C\u00e1mara","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, IDIBAPS, CIBERNED (CB06\/05\/0018-ISCIII), ERN-RND, Institut Cl\u00ednic de Neuroci\u00e8ncies UBNeuro (Maria de Maeztu Excellence Centre), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaroslau","family":"Compta","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, IDIBAPS, CIBERNED (CB06\/05\/0018-ISCIII), ERN-RND, Institut Cl\u00ednic de Neuroci\u00e8ncies UBNeuro (Maria de Maeztu Excellence Centre), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Carre\u00f1o","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Department of Neurology, Hospital Clinic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jose","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, IDIBAPS, CIBERNED (CB06\/05\/0018-ISCIII), ERN-RND, Institut Cl\u00ednic de Neuroci\u00e8ncies UBNeuro (Maria de Maeztu Excellence Centre), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"S\u00e1nchez-Valle","sequence":"additional","affiliation":[{"name":"Neurology Department, Clinical Institute of Neurosciences, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"},{"name":"Biomedical Research Institute August Pi i Sunyer (IDIBAPS), Hospital Clinic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-1199","authenticated-orcid":false,"given":"Irene","family":"Madrigal","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics Department, Hospital Clinic of Barcelona, IDIBAPS (Institut de Investigacions Biom\u00e8diques August Pi I Sunyer), 08036 Barcelona, Spain"},{"name":"CIBER of Rare Diseases (CIBERER), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100464","DOI":"10.1016\/j.ymgmr.2019.100464","article-title":"Next generation sequencing for clinical diagnostics: Five year experience of an academic laboratory","volume":"19","author":"Hartman","year":"2019","journal-title":"Mol. 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