{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:53:25Z","timestamp":1756385605858,"version":"3.40.5"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["No. 10 in 2009"],"award-info":[{"award-number":["No. 10 in 2009"]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>R3HDM1 (R3H domain containing 1) is an uncharacterized RNA\u2010binding protein that is highly expressed in the human cerebral cortex. We report the first case of a 12\u2010year\u2010old Japanese male with haploinsufficiency of <jats:italic>R3HDM1<\/jats:italic>. He presented with mild intellectual disability (ID) and developmental delay. He had a pericentric inversion of 46,XY,inv(2)(p16.1q21.3)dn with breakpoints in intron 19 of <jats:italic>R3HDM1<\/jats:italic> (2q21.3) and the intergenic region (2p16.1). The <jats:italic>R3HDM1<\/jats:italic> levels in his lymphoblastoid cells were reduced to approximately half that of the healthy controls. However, the expression of <jats:italic>MIR128\u20101<\/jats:italic>, in intron 18 of <jats:italic>R3HDM1<\/jats:italic>, was not affected via the pericentric inversion. Knockdown of R3HDM1 in mouse embryonic hippocampal neurons suppressed dendritic growth and branching. Notably, the Database of Genomic Variants reported the case of a healthy control with a 488\u2010kb deletion that included both <jats:italic>R3HDM1<\/jats:italic> and <jats:italic>MIR128<\/jats:italic>\u2010<jats:italic>1<\/jats:italic>. miR\u2010128 has been reported to inhibit dendritic growth and branching in mouse brain neurons, which directly opposes the novel functions of R3HDM1. These findings suggest that deleting both <jats:italic>R3HDM1<\/jats:italic> and <jats:italic>MIR128<\/jats:italic>\u2010<jats:italic>1<\/jats:italic> alleviates the symptoms of the disease caused by loss\u2010of\u2010function mutations in <jats:italic>R3HDM1<\/jats:italic> only. Thus, haploinsufficiency of <jats:italic>R3HDM1<\/jats:italic> in the patient may be the cause of the mild ID due to the genetic imbalance between <jats:italic>R3HDM1<\/jats:italic> and <jats:italic>MIR128\u20101<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/ajmg.a.62173","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T13:40:11Z","timestamp":1616420411000},"page":"1776-1786","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp><i>R3HDM1<\/i><\/scp> haploinsufficiency is associated with mild intellectual disability"],"prefix":"10.1002","volume":"185","author":[{"given":"Daisuke","family":"Fukushi","sequence":"first","affiliation":[{"name":"Department of Genetics Institute for Developmental Research, Aichi Developmental Disability Center  Kasugai 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