{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:44:40Z","timestamp":1792071880090,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515111198"],"award-info":[{"award-number":["2022A1515111198"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical &amp; Exp Dental Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI; OMIM#130900) is a hereditary enamel defect caused by truncation mutations in\n                      <jats:italic>FAM83H<\/jats:italic>\n                      , though the underlying pathogenic mechanisms remain incompletely understood. This study aimed to identify novel\n                      <jats:italic>FAM83H<\/jats:italic>\n                      mutations in a Chinese family with ADHCAI and to investigate their functional consequences on enamel formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>A three\u2010generation ADHCAI family underwent clinical and genetic evaluation. Whole\u2010exome sequencing and Sanger sequencing were used for mutation identification. The proband's enamel was analyzed by scanning electron microscopy with energy\u2010dispersive X\u2010ray spectroscopy (SEM\u2010EDX). Structural impacts of the mutation were predicted bioinformatically (PSIPRED, SWISS\u2010MODEL). Patient\u2010derived periodontal ligament cells (PDLCs) were assessed by Western blot, immunofluorescence, and quantitative real\u2010time PCR for key enamel matrix proteins (AMELX, AMBN, ENAM) and osteogenic markers (RUNX2, ALP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel heterozygous nonsense mutation (c.1819G&gt;T, p.(Glu607*)) in\n                      <jats:italic>FAM83H<\/jats:italic>\n                      was identified, resulting in a C\u2010terminally truncated protein lacking 573 residues that mislocalizes from the cytoplasm to the nucleus. SEM\u2010EDX revealed disorganized enamel ultrastructure, a reduced calcium\u2010to\u2010phosphorus ratio, and increased porosity. Functional analysis in PDLCs showed coordinated downregulation of enamel matrix proteins and osteogenic markers, indicating a dual regulatory role for FAM83H in biomineralization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings are consistent with the \u201cpresecretory pathogenesis\u201d model for ADHCAI, wherein nuclear\u2010mislocalized truncated FAM83H may disrupt enamel mineralization partly through transcriptional suppression of matrix components. This expands the\n                      <jats:italic>FAM83H<\/jats:italic>\n                      mutational spectrum, offers preliminary mechanistic insight, and suggests potential targets for pre\u2010eruptive therapeutic strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cre2.70431","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:26:08Z","timestamp":1786645568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel FAM83H Truncation Mutation Disrupts Enamel Mineralization in Autosomal Dominant Hypocalcified Amelogenesis Imperfecta"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9463-2659","authenticated-orcid":false,"given":"Yue","family":"Wang","sequence":"first","affiliation":[{"name":"Guanghua School and Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research Sun Yat\u2010sen University Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-5829","authenticated-orcid":false,"given":"Hongfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Guanghua School and Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research Sun Yat\u2010sen University Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4345-1418","authenticated-orcid":false,"given":"Jiyong","family":"Lai","sequence":"additional","affiliation":[{"name":"Ganzhou Weile Dental Hospital Ganzhou Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5427-0321","authenticated-orcid":false,"given":"Xueqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Guanghua School and Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research Sun Yat\u2010sen University Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0136-0802","authenticated-orcid":false,"given":"Yanyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Guanghua School and Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Institute of Stomatological Research Sun Yat\u2010sen University Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/children9030362"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1902"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1130175"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20160277"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514547272"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000252801"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200409077"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016350902973685"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/humu\/8942542"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01112.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-263X.2011.01142.x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M710565200"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2591.2009.01617.x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.70108"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37406"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.09.020"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep34472"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.129684"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13071272"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20789"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510389177"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-020-01199-z"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12926"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272775"},{"issue":"12","key":"e_1_2_11_26_1","first-page":"1680","article-title":"Missense Mutation in Fam83H Gene in Iranian Patients With Amelogenesis Imperfecta","volume":"43","author":"Pourhashemi S. 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