{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:23:20Z","timestamp":1773833000611,"version":"3.50.1"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Science Foundation of Wuhan Health and Family Planning Commission","award":["grant number:WZ22Q33"],"award-info":[{"award-number":["grant number:WZ22Q33"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>NUDT2 is an enzyme important for maintaining the intracellular level of the diadenosine tetraphosphate (Ap4A). Bi-allelic loss of function variants in <jats:italic>NUDT2<\/jats:italic> has recently been reported as a rare cause of intellectual disability (ID). Herein, we describe a Chinese girl with ID, attention deficit hyperactivity disorder (ADHD), and motor delays with abnormal walking posture and difficulty climbing stairs, who bears compound heterozygous variants c.34\u00a0C\u2009&gt;\u2009T (p.R12*) and c.194T\u2009&gt;\u2009G (p.I65R) in <jats:italic>NUDT2<\/jats:italic>. Homozygous variants c.34\u00a0C\u2009&gt;\u2009T (p.R12*) or c.186del (p.A63Qfs*3) in <jats:italic>NUDT2<\/jats:italic> were previously reported to cause ID. This is the first patient with ID due to compound heterozygous variants in <jats:italic>NUDT2<\/jats:italic> and p.I65R is a novel missense variant. This study enriched the genotype and phenotype of <jats:italic>NUDT2-<\/jats:italic>related ID and supported the critical developmental involvement of <jats:italic>NUDT2.<\/jats:italic><\/jats:p>","DOI":"10.1186\/s12887-024-04542-3","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T06:02:34Z","timestamp":1705644154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The first case of intellectual disability caused by novel compound heterozygosity for NUDT2 variants"],"prefix":"10.1186","volume":"24","author":[{"given":"Bo","family":"Bi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyue","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangcan","family":"Ming","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"issue":"6","key":"4542_CR1","doi-asserted-by":"publisher","first-page":"558","DOI":"10.7861\/clinmedicine.17-6-558","volume":"17","author":"P Vasudevan","year":"2017","unstructured":"Vasudevan P, Suri M. A clinical approach to developmental delay and intellectual disability. Clin Med (Lond). 2017;17(6):558\u201361. https:\/\/doi.org\/10.7861\/clinmedicine.17-6-558.","journal-title":"Clin Med (Lond)"},{"issue":"6","key":"4542_CR2","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1097\/YCO.0000000000000456","volume":"31","author":"N Bass","year":"2018","unstructured":"Bass N, Skuse D. Genetic testing in children and adolescents with intellectual disability. Curr Opin Psychiatry. 2018;31(6):490\u20135. https:\/\/doi.org\/10.1097\/YCO.0000000000000456.","journal-title":"Curr Opin Psychiatry"},{"issue":"1","key":"4542_CR3","doi-asserted-by":"publisher","first-page":"6918","DOI":"10.1038\/s41467-021-27239-y","volume":"12","author":"BT Laudenbach","year":"2021","unstructured":"Laudenbach BT, Krey K, Emslander Q, et al. NUDT2 initiates viral RNA degradation by removal of 5\u2019-phosphates. Nat Commun. 2021;12(1):6918. https:\/\/doi.org\/10.1038\/s41467-021-27239-y.","journal-title":"Nat Commun"},{"issue":"12","key":"4542_CR4","doi-asserted-by":"publisher","first-page":"6788","DOI":"10.1093\/nar\/gkaa402","volume":"48","author":"S Sharma","year":"2020","unstructured":"Sharma S, Grudzien-Nogalska E, Hamilton K, et al. Mammalian nudix proteins cleave nucleotide metabolite caps on RNAs. Nucleic Acids Res. 2020;48(12):6788\u201398. https:\/\/doi.org\/10.1093\/nar\/gkaa402.","journal-title":"Nucleic Acids Res"},{"key":"4542_CR5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.cellsig.2017.01.015","volume":"32","author":"O Kwon","year":"2017","unstructured":"Kwon O, Kwak D, Ha SH, et al. Nudix-type motif 2 contributes to cancer proliferation through the regulation of rag GTPase-mediated mammalian target of rapamycin complex 1 localization. Cell Signal. 2017;32:24\u201335. https:\/\/doi.org\/10.1016\/j.cellsig.2017.01.015.","journal-title":"Cell Signal"},{"issue":"5","key":"4542_CR6","doi-asserted-by":"publisher","first-page":"e0154674","DOI":"10.1371\/journal.pone.0154674","volume":"11","author":"AS Marriott","year":"2016","unstructured":"Marriott AS, Vasieva O, Fang Y, Copeland NA, McLennan AG, Jones NJ. NUDT2 disruption elevates Diadenosine Tetraphosphate (Ap4A) and down-regulates Immune Response and Cancer Promotion genes. PLoS ONE. 2016;11(5):e0154674. https:\/\/doi.org\/10.1371\/journal.pone.0154674.","journal-title":"PLoS ONE"},{"issue":"8","key":"4542_CR7","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1002\/ijc.25505","volume":"128","author":"K Oka","year":"2011","unstructured":"Oka K, Suzuki T, Onodera Y, et al. Nudix-type motif 2 in human breast carcinoma: a potent prognostic factor associated with cell proliferation. Int J Cancer. 2011;128(8):1770\u201382. https:\/\/doi.org\/10.1002\/ijc.25505.","journal-title":"Int J Cancer"},{"issue":"4","key":"4542_CR8","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/mp.2016.113","volume":"22","author":"S Anazi","year":"2017","unstructured":"Anazi S, Maddirevula S, Faqeih E, et al. Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. Mol Psychiatry. 2017;22(4):615\u201324. https:\/\/doi.org\/10.1038\/mp.2016.113.","journal-title":"Mol Psychiatry"},{"issue":"3\u20134","key":"4542_CR9","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1111\/cge.13386","volume":"94","author":"H Yavuz","year":"2018","unstructured":"Yavuz H, Bertoli-Avella AM, Alfadhel M, et al. A founder nonsense variant in NUDT2 causes a recessive neurodevelopmental disorder in Saudi arab children. 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Genet Med. 2015;17(5):405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","journal-title":"Genet Med"}],"container-title":["BMC Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-024-04542-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12887-024-04542-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-024-04542-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T06:02:56Z","timestamp":1705644176000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpediatr.biomedcentral.com\/articles\/10.1186\/s12887-024-04542-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,19]]},"references-count":15,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4542"],"URL":"https:\/\/doi.org\/10.1186\/s12887-024-04542-3","relation":{},"ISSN":["1471-2431"],"issn-type":[{"value":"1471-2431","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,19]]},"assertion":[{"value":"16 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2024","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 patient was admitted to the rehabilitation department of Wuhan Children\u2019s Hospital in September 2021. All procedures performed in studies involving human participants were conformed to the ethical guidelines of the 1975 Declaration of Helsinki and approved by the Ethical Committee of Wuhan Children\u2019s Hospital (Ethical approval number: 2022R043-E01). Written informed consent for genetic analysis was obtained from the parents of the affected individual.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient\u2019s parents for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"60"}}