{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T04:40:05Z","timestamp":1751604005899,"version":"3.41.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Paganini-Miozzo syndrome (MRXSPM) is a globally rare disease caused by hemizygous mutations in the <jats:italic>HS6ST2<\/jats:italic> gene on chromosome Xq26. This study presents the first case of MRXSPM in China, meanwhile the fourth case worldwide. The proband was admitted to the hospital due to developmental delay. Whole exome sequencing (WES) revealed a novel variant, c.764C&amp;gt;A (p.Pro255Glu) missense mutation in the <jats:italic>HS6ST2<\/jats:italic> gene. Brain CT showed mild lateral ventricular enlargement, and electroencephalogram showed diffuse spikes and waves. Biochemical tests indicated significantly elevated transaminases, blood lactate values, and lactate\/pyruvate values. Bioinformatics predictions suggest that this mutation may affect the thermal stability of the HS6ST2 protein. The amino acid where the mutation c.764C&amp;gt;A p.P255Q occurs is conserved across multiple species, specifically being proline in 13 species. <jats:italic>In vitro<\/jats:italic> cell experiments demonstrated that this mutant can impact the expression of HS6ST2 protein at post-transcriptional level. Comparison with previously reported cases revealed that different mutations might lead to different alternations in the function of HS6ST2 protein, resulting in distinct clinical phenotypes.<\/jats:p>","DOI":"10.3389\/fgene.2025.1515260","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T04:10:25Z","timestamp":1751602225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel missense variant of HS6ST2 gene in Paganini-Miozzo syndrome with a rare neurodevelopmental and Endocrine phenotypes"],"prefix":"10.3389","volume":"16","author":[{"given":"Meiling","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fucheng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1038\/nature05817","article-title":"Heparan sulphate proteoglycans fine\u2010tune mammalian physiology","volume":"446","author":"Bishop","year":"2007","journal-title":"Nature."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1002\/dvdy.24142","article-title":"Role of heparan sulfate proteoglycans in optic disc and stalk morphogenesis","volume":"243","author":"Cai","year":"2014","journal-title":"Dev. 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