{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T06:40:34Z","timestamp":1776667234424,"version":"3.51.2"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Community Genet"],"DOI":"10.1007\/s12687-026-00870-2","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T03:19:41Z","timestamp":1774063181000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic insights: proband- only exome sequencing in pediatric neurological disorders"],"prefix":"10.1007","volume":"17","author":[{"given":"Komal","family":"Uppal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Himani","family":"Kaushik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5144-5577","authenticated-orcid":false,"given":"Meenakshi Bothra","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil Kumar","family":"Polipalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seema","family":"Kapoor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"issue":"1","key":"870_CR1","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13023-016-0474-3","volume":"11","author":"A Al-Shamsi","year":"2016","unstructured":"Al-Shamsi A, Hertecant JL, Souid AK, Al-Jasmi FA (2016) Whole exome sequencing diagnosis of inborn errors of metabolism and other disorders in United Arab Emirates. Orphanet J Rare Dis 11(1):94","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"870_CR2","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s13023-022-02213-z","volume":"17","author":"MI Alvarez-Mora","year":"2022","unstructured":"Alvarez-Mora MI, S\u00e1nchez A, Rodr\u00edguez-Revenga L, Corominas J, Rabionet R, Puig S et al (2022) Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders. Orphanet J Rare Dis 17(1):60","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"870_CR3","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/cge.12793","volume":"91","author":"JS Amos","year":"2017","unstructured":"Amos JS, Merritt JL 2nd, Tobias JD, Renaud DL, Wangler MF (2017) Autosomal recessive mutations in THOC6 cause intellectual disability: Syndrome delineation requiring forward and reverse phenotyping. Clin Genet 91(1):92\u201399","journal-title":"Clin Genet"},{"key":"870_CR4","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/1750-1172-8-62","volume":"8","author":"CL Beaulieu","year":"2013","unstructured":"Beaulieu CL, Majewski J, Schwartzentruber J, Samuels ME, Fernandez BA, Bernier FP et al (2013) Intellectual disability associated with a homozygous missense mutation in THOC6. Orphanet J Rare Dis 8:62","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"870_CR5","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/cge.13946","volume":"100","author":"T Brunet","year":"2021","unstructured":"Brunet T, Jech R, Brugger M, Kovacs R, Alhaddad B, Leszinski G et al (2021) De novo variants in neurodevelopmental disorders: experiences from a tertiary care center. Clin Genet 100(1):14\u201328. https:\/\/doi.org\/10.1111\/cge.13946","journal-title":"Clin Genet"},{"issue":"5","key":"870_CR6","doi-asserted-by":"publisher","first-page":"104730","DOI":"10.1016\/j.ejmg.2023.104730","volume":"66","author":"RP Chand","year":"2023","unstructured":"Chand RP, Wankhede V, Vaidya V, Iyer AS, Shelke M, Aggarwal S et al (2023) Proband only exome sequencing in 403 Indian children with neurodevelopmental disorders: Diagnostic yield, utility and challenges in a resource-limited setting. Eur J Med Genet 66(5):104730","journal-title":"Eur J Med Genet"},{"issue":"2","key":"870_CR7","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1212\/CPJ.0000000000000239","volume":"6","author":"BL Fogel","year":"2016","unstructured":"Fogel BL, Satya-Murti S, Cohen BH (2016) Clinical exome sequencing in neurologic disease. Neurol Clin Pract 6(2):164\u2013176","journal-title":"Neurol Clin Pract"},{"issue":"4","key":"870_CR8","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1111\/cge.13720","volume":"97","author":"NO FroukhT","year":"2020","unstructured":"FroukhT NO, Al Hait SA, Laugwitz L, Sommerfeld J, Sturm M et al (2020) Genetic basis of neurodevelopmental disorders in 103 Jordanian families. Clin Genet 97(4):621\u2013627. https:\/\/doi.org\/10.1111\/cge.13720","journal-title":"Clin Genet"},{"key":"870_CR9","doi-asserted-by":"publisher","first-page":"782685","DOI":"10.3389\/fgene.2022.782685","volume":"13","author":"F Ghorbani","year":"2022","unstructured":"Ghorbani F, Alimohamed MZ, Vilacha JF, Van Dijk KK, De Boer-Bergsma J, Fokkens MR et al (2022) Feasibility of follow-up studies and reclassification in spinocerebellar ataxia gene variants of unknown significance. Front Genet 13:782685","journal-title":"Front Genet"},{"issue":"3","key":"870_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2019.103742","volume":"63","author":"N Gupta","year":"2020","unstructured":"Gupta N, Sharma A, Srivastava S, Verma IC (2020) First report of THOC6-related intellectual disability (Beaulieu Boycott Innes syndrome) in two siblings from India. Eur J Med Genet 63(3):103742","journal-title":"Eur J Med Genet"},{"issue":"2","key":"870_CR11","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1177\/1073858417705840","volume":"24","author":"RM Hauser","year":"2018","unstructured":"Hauser RM, Henshall DC, Lubin FD (2018) The epigenetics of epilepsy and its progression. Neuroscientist 24(2):186\u2013200","journal-title":"Neuroscientist"},{"key":"870_CR12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.pediatrneurol.2019.02.017","volume":"99","author":"SH Kim","year":"2019","unstructured":"Kim SH, Kim B, Lee JS et al (2019) Proband-only clinical exome sequencing for neurodevelopmental disabilities. Pediatr Neurol 99:47\u201354","journal-title":"Pediatr Neurol"},{"issue":"12","key":"870_CR13","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1038\/gim.2018.51","volume":"20","author":"S Kong","year":"2018","unstructured":"Kong S, Lee I, Liu X, Hirschhorn JN, Mandl KD (2018) Measuring coverage and accuracy of whole-exome sequencing in clinical context. Genet Med 20(12):1617\u20131626","journal-title":"Genet Med"},{"issue":"12","key":"870_CR14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209185","volume":"13","author":"DS Marchuk","year":"2018","unstructured":"Marchuk DS, Crooks K, Strande N, Kaiser-Rogers K, Milko LV, Brandt A et al (2018) Increasing the diagnostic yield of exome sequencing by copy number variant analysis. PLoS One 13(12):e0209185","journal-title":"PLoS One"},{"issue":"6","key":"870_CR15","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1093\/hmg\/ddy391","volume":"28","author":"F Mattioli","year":"2019","unstructured":"Mattioli F, Schaefer E, Magee A, Mark P, Mancini GM, Dieterich K et al (2019) Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability. Hum Mol Genet 28(6):952\u2013960","journal-title":"Hum Mol Genet"},{"key":"870_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2023.100866","volume":"25","author":"D Miller","year":"2023","unstructured":"Miller D, Lee K, Abul-Husn N, Amendola L, Brothers K, Chung W et al (2023) ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med 25:100866","journal-title":"Genet Med"},{"issue":"2","key":"870_CR17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2478\/bjmg-2020-0028","volume":"23","author":"OY Muthaffar","year":"2020","unstructured":"Muthaffar OY (2020) The utility of whole exome sequencing in diagnosing pediatric neurological disorders. Balkan J Med Genet 23(2):17\u201324","journal-title":"Balkan J Med Genet"},{"key":"870_CR18","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23946","author":"KJ Ngo","year":"2020","unstructured":"Ngo KJ, Rexach JE, Lee H, Petty LE, Perlman S, Valera JM et al (2020) A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders. Hum Mutat. https:\/\/doi.org\/10.1002\/humu.23946","journal-title":"Hum Mutat"},{"issue":"1","key":"870_CR19","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.ajog.2021.07.014","volume":"226","author":"ME Norton","year":"2022","unstructured":"Norton ME, Ziffle JV, Lianoglou BR, Hodoglugil U, Devine WP, Sparks TN (2022) Exome sequencing vs targeted gene panels for the evaluation of nonimmune hydrops fetalis. Am J Obstet Gynecol 226(1):128. https:\/\/doi.org\/10.1016\/j.ajog.2021.07.014","journal-title":"Am J Obstet Gynecol"},{"key":"870_CR20","doi-asserted-by":"publisher","first-page":"19099","DOI":"10.1038\/s41598-021-98646-w","volume":"11","author":"B Pode-Shakked","year":"2021","unstructured":"Pode-Shakked B, Barel O, Singer A, Regev M, Poran H, Eliyahu A et al (2021) A single-center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies. Sci Rep 11:19099","journal-title":"Sci Rep"},{"key":"870_CR21","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/gim.2014.160","volume":"17","author":"K Retterer","year":"2015","unstructured":"Retterer K, Scuffins J, Schmidt D, Lewis R, Pineda-Alvarez D, Stafford A et al (2015) Assessing copy number from exome sequencing and exome array CGH based on CNV spectrum in a large clinical cohort. Genet Med 17:623\u2013629","journal-title":"Genet Med"},{"issue":"5","key":"870_CR22","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) 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. Genet Med 17(5):405\u2013424","journal-title":"Genet Med"},{"key":"870_CR23","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1101\/gad.300704","volume":"18","author":"G Schotta","year":"2004","unstructured":"Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G et al (2004) A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev 18:1251\u20131262","journal-title":"Genes Dev"},{"key":"870_CR24","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s10020-022-00464-x","volume":"28","author":"GH Seo","year":"2022","unstructured":"Seo GH, Lee H, Lee J, Han H, Cho YK, Kim M et al (2022) Diagnostic performance of automated, streamlined, daily updated exome analysis in patients with neurodevelopmental delay. Mol Med 28:38","journal-title":"Mol Med"},{"key":"870_CR25","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1186\/s12883-023-03341-0","volume":"23","author":"J ShethF, Shah","year":"2023","unstructured":"Sheth F, Shah J, Jain D, Shah S, Patel H, Patel K et al (2023) Comparative yield of molecular diagnostic algorithms for autism spectrum disorder diagnosis in India: Evidence supporting whole exome sequencing as first-tier test. BMC Neurol 23:292. https:\/\/doi.org\/10.1186\/s12883-023-03341-0","journal-title":"BMC Neurol"},{"issue":"6","key":"870_CR26","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.4103\/0028-3886.333475","volume":"69","author":"H Sheth","year":"2021","unstructured":"Sheth H, Pancholi D, Bhavsar R, Mannan AU, Ganapathy A, Chowdhury M et al (2021) Assessing utility of clinical exome sequencing in diagnosis of rare idiopathic neurodevelopmental disorders in Indian population. Neurol India 69(6):1729\u20131736","journal-title":"Neurol India"},{"issue":"11","key":"870_CR27","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1038\/s41436-019-0554-6","volume":"21","author":"S Srivastava","year":"2019","unstructured":"Srivastava S, Love-Nichols JA, Dies KA, Ledbetter DH, Martin CL, Chung WK et al (2019) Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med 21(11):2413\u201321","journal-title":"Genet Med"},{"issue":"1","key":"870_CR28","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s11689-019-9270-4","volume":"11","author":"J Trinh","year":"2019","unstructured":"Trinh J, Kandaswamy KK, Werber M, Weiss MER, Oprea G, Kishore S et al (2019) Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders. J Neurodev Disord 11(1):11","journal-title":"J Neurodev Disord"},{"issue":"8","key":"870_CR29","doi-asserted-by":"publisher","first-page":"452","DOI":"10.52403\/ijhsr.20240852","volume":"14","author":"K Uppal","year":"2024","unstructured":"Uppal K, Rana L, Kaushik H, Polipalli S, Kumar S, Kapoor S (2024) Clinical phenotype of a rare pathogenic variant in STXBP1 gene. Int J Health Sci Res 14(8):452\u2013456. https:\/\/doi.org\/10.52403\/ijhsr.20240852","journal-title":"Int J Health Sci Res"},{"issue":"2","key":"870_CR30","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.ejpn.2014.12.014","volume":"19","author":"KJM Van Nimwegen","year":"2015","unstructured":"Van Nimwegen KJM, Schieving JH, Willemsen MAA, Veltman JA, van der Burg S, van der Wilt GJ et al (2015) The diagnostic pathway in complex paediatric neurology: A cost analysis. Eur J Paediatr Neurol 19(2):233\u2013239","journal-title":"Eur J Paediatr Neurol"},{"issue":"3","key":"870_CR31","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200133","volume":"10","author":"S Watson","year":"2024","unstructured":"Watson S, Ngo KJ, Stevens HA, Wong DY, Kim J, Song Y et al (2024) Cross-sectional analysis of exome sequencing diagnosis in patients with neurologic phenotypes facing barriers to clinical testing. Neurol Genet 10(3):e200133","journal-title":"Neurol Genet"},{"issue":"1","key":"870_CR32","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13023-024-03056-6","volume":"19","author":"M Wayhelova","year":"2024","unstructured":"Wayhelova M, Vallova V, Broz P, Mikulasova A, Smetana J, Filkova HD et al (2024) Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders. Orphanet J Rare Dis 19:41","journal-title":"Orphanet J Rare Dis"},{"issue":"18","key":"870_CR33","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1001\/jama.2014.14601","volume":"312","author":"Y Yang","year":"2014","unstructured":"Yang Y, Muzny DM, Xia F, Niu Z, Person R et al (2014) Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312(18):1870\u20131879","journal-title":"JAMA"}],"container-title":["Journal of Community Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12687-026-00870-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12687-026-00870-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12687-026-00870-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:45:46Z","timestamp":1776663946000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12687-026-00870-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,21]]},"references-count":33,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["870"],"URL":"https:\/\/doi.org\/10.1007\/s12687-026-00870-2","relation":{},"ISSN":["1868-6001"],"issn-type":[{"value":"1868-6001","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,21]]},"assertion":[{"value":"9 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39"}}