{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:53:18Z","timestamp":1777499598136,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Lesch-Nyhan disease (LND) is a rare disorder involving pathogenic variants in the <jats:italic>HPRT1<\/jats:italic> gene encoding the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) that result in hyperuricemia, intellectual disability, dystonic movement disorder, and compulsive self-mutilation. The purpose of the present study was to characterize the genetic basis of LND and describe its phenotypic heterogeneity by identifying the variation in the <jats:italic>HPRT1<\/jats:italic> gene in a cohort of Chinese LND patients.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The median age at diagnosis was 31\u00a0mo (interquartile range (IQR): 7\u201376\u00a0mo), and the initial manifestations were mainly head control weakness and motor development delay. The median age of self-mutilation behavior onset was 19\u00a0mo (IQR: 17\u201324\u00a0mo), and all patients were required to travel in a wheelchair and fall into the predicament of compulsive self-harm behavior. There were two patients whose blood uric acid levels were normal for their high urinary acid excretion fraction without taking uric acid-lowering drugs. Seven different pathogenic variants of the <jats:italic>HPRT1<\/jats:italic> gene were identified among eight independent pedigrees, including four novel mutations [c.299 (exon 3) T &amp;gt; A; loss (exon: 6) 84\u00a0bp; c.277_281delATTGC; c.468_470delGAT]. The pathogenic variant sites were mainly concentrated in exon 3, and truncating mutations (including frameshift mutations and nonsense mutations) were the most common genetic variant types (5\/7, 71.4%).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The present study described the phenotypic and molecular spectrum of LND in eight Chinese families, including four novel mutations, which expands our understanding of LND.<\/jats:p>","DOI":"10.3389\/fgene.2022.868942","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T05:06:55Z","timestamp":1650949615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Description of the Molecular and Phenotypic Spectrum of Lesch-Nyhan Disease in Eight Chinese Patients"],"prefix":"10.3389","volume":"13","author":[{"given":"Lu","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijun","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haidong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Hua","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/0278-5846(96)00059-0","article-title":"Risperidone Antagonism of Self-Mutilation in a Lesch-Nyhan Patient","volume":"20","author":"Allen","year":"1996","journal-title":"Prog. 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