{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T02:10:09Z","timestamp":1772763009358,"version":"3.50.1"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Research and Technology\/National Research and Innovation Agency of the Republic of Indonesia","award":["018\/E5\/PG.02.00.PT\/2022"],"award-info":[{"award-number":["018\/E5\/PG.02.00.PT\/2022"]}]},{"name":"Ministry of Research and Technology\/National Research and Innovation Agency of the Republic of Indonesia","award":["2137\/UN1\/DITLIT\/Dit-Lit\/PT.01.03\/2023"],"award-info":[{"award-number":["2137\/UN1\/DITLIT\/Dit-Lit\/PT.01.03\/2023"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Neurogenetic disorders (NGDs) are complex Mendelian disorders that affect the neurological system. A molecular diagnosis will provide more information about pathophysiology, prognosis, and therapy, including future genetic therapy options. Whole-Exome Sequencing (WES) can rapidly discover the genetic basis in NGDs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>The purpose of this study was to assess the WES results and its value in diagnosing pediatric NGDs, especially those with unspecified clinical features.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A retrospective chart review was performed from May 2021- February 2023 in Dr. Sardjito General Hospital, a tertiary referral hospital in Yogyakarta, Indonesia. WES proband only was conducted on children aged 0 to 17 years old who met one or more of the following criteria: (1) epileptic encephalopathy and familial epilepsy; (2) complex neurodevelopmental phenotypes; (3) leukodystrophy; (4) movement disorders; and (5) neurocutaneous disorder. The WES was conducted in the certified laboratory, 3Billion, in Seoul, Korea.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>The diagnosis yield of WES in our study was 45% (9\/20). We identified nine positive results, including eight pathogenic single nucleotide variants (SNVs) in 8 genes (<jats:italic>KCNQ2<\/jats:italic>, <jats:italic>ARSA<\/jats:italic>, <jats:italic>UBE3A<\/jats:italic>, <jats:italic>IRF2BPL<\/jats:italic>, <jats:italic>ATM<\/jats:italic>, <jats:italic>MECP2<\/jats:italic>, <jats:italic>TSC2<\/jats:italic>, and <jats:italic>NF1<\/jats:italic>), and one variant with uncertain significance (VUS) in the <jats:italic>ADK<\/jats:italic> gene that has not been able to explain the observed clinical features. Of the nine patients with positive WES results, five had missense mutations, three frameshift mutations, and one nonsense mutation. Additionally, we identified two suggestive copy number variants (CNVs) in <jats:italic>15q11<\/jats:italic>.<jats:italic>2q13<\/jats:italic>.<jats:italic>1<\/jats:italic> and <jats:italic>1p31<\/jats:italic>.<jats:italic>3<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Whole-Exome Sequencing is an essential diagnostic tool for pediatric NGDs, especially those with unspecified clinical features. It ends multi-year diagnostic odysseys, provides personalized medicine therapy, and optimizes genetic counselling for these families.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0293113","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T17:38:58Z","timestamp":1698255538000},"page":"e0293113","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of the genetic basis of pediatric neurogenetic disorders at a tertiary referral hospital in Indonesia: Contribution of whole exome 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Wulan","family":"Wijayanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2571-8310","authenticated-orcid":true,"given":"Elisabeth Siti","family":"Herini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"pone.0293113.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pediatrneurol.2016.07.010","article-title":"Treatment of Neurogenetic Developmental Conditions: From 2016 into the Future","volume":"65","author":"CDM van Karnebeek","year":"2016","journal-title":"Pediatric Neurology"},{"key":"pone.0293113.ref002","doi-asserted-by":"crossref","first-page":"695","DOI":"10.3390\/genes12050695","article-title":"NGS-Based Diagnosis of Treatable Neurogenetic Disorders in Adults: Opportunities and Challenges","volume":"12","author":"J-M 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