{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:01:54Z","timestamp":1780038114879,"version":"3.53.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":147,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000875"],"award-info":[{"award-number":["82000875"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Nance\u2013Horan syndrome (NHS) is a rare X\u2010linked genetic disorder characterized by congenital cataracts, dental anomalies, and neurodevelopmental impairments, caused by mutations in the\n                    <jats:italic>NHS<\/jats:italic>\n                    gene. In this study, two novel\n                    <jats:italic>NHS<\/jats:italic>\n                    mutations, c.3847C&gt;T and c.2519_2520del, were identified in two unrelated Chinese Han families, and their pathogenic molecular mechanisms were elucidated. Functional analyses revealed that the c.3847C&gt;T mutation exerts a dual pathogenic effect: It disrupts extracellular matrix homeostasis by downregulating\n                    <jats:italic>COL4A1<\/jats:italic>\n                    and upregulating\n                    <jats:italic>MMP9<\/jats:italic>\n                    , and it triggers oxidative stress, evidenced by elevated ROS levels, altered BAX\/BCL\u20102 ratio, and reduced\n                    <jats:italic>GPX4<\/jats:italic>\n                    expression, ultimately leading to apoptosis and impaired cell migration. In contrast, the c.2519_2520del mutation primarily impairs mitochondrial function, as indicated by decreased membrane potential, reduced ATP production, and downregulation of\n                    <jats:italic>ALDH3A1<\/jats:italic>\n                    and\n                    <jats:italic>SOD2<\/jats:italic>\n                    . This mitochondrial dysfunction is further exacerbated by suppressed\n                    <jats:italic>PGC-1\u03b1<\/jats:italic>\n                    expression, contributing to metabolic disturbances, and by\n                    <jats:italic>p21<\/jats:italic>\n                    \u2010mediated cell cycle arrest. These findings, for the first time, demonstrate that distinct types of\n                    <jats:italic>NHS<\/jats:italic>\n                    mutations cause disease via divergent mechanisms, extracellular matrix disruption versus mitochondrial dysfunction, providing molecular insights into the clinical phenotypic heterogeneity of NHS and laying a theoretical foundation for the development of mutation\u2010specific precision therapies.\n                  <\/jats:p>","DOI":"10.1155\/humu\/3739907","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:06:22Z","timestamp":1780034782000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Pathogenic Mechanisms of Two Novel NHS Mutations Identified in Chinese Han Families With Nance\u2013Horan Syndrome"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8092-8719","authenticated-orcid":false,"given":"Li","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangying","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37963"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2100"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-023-03029-4"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11091150"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2024.148268"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-018-0725-3"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/13816810.2011.634881"},{"key":"e_1_2_11_8_2","volume-title":"Scientific Reports","author":"Li H.","year":"2018"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-024-01638-3"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01264-6"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201671"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B1300321"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-025-03933-z"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112142-20231113-00230"},{"key":"e_1_2_11_15_2","doi-asserted-by":"crossref","unstructured":"BerrierA. 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MukherjeeS. MukhiD. DhillonP. AbediniA. DavisJ. G. ChellappaK. ChenB. BaurJ. A. andSusztakK. Nad+ Precursor Supplementation Prevents Mtrna\/Rig-I-Dependent Inflammation During Kidney Injury Nature Metabolism 2023 5 414\u2013430.","DOI":"10.1038\/s42255-023-00761-7"},{"key":"e_1_2_11_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2022.129381"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/3739907","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/humu\/3739907","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/3739907","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:06:29Z","timestamp":1780034789000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/humu\/3739907"}},"subtitle":[],"editor":[{"given":"Harleen","family":"Khatra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/humu\/3739907"],"URL":"https:\/\/doi.org\/10.1155\/humu\/3739907","archive":["Portico"],"relation":{},"ISSN":["1059-7794","1098-1004"],"issn-type":[{"value":"1059-7794","type":"print"},{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"3739907"}}