{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T15:09:55Z","timestamp":1778944195543,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":135,"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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study is aimed at investigating the genetic defects and clinical features of Chinese children with\n                      <jats:italic>SLC16A2<\/jats:italic>\n                      variants and at exploring the effects of mutant MCT8 on protein expression and subcellular localization through in vitro experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Children with intellectual disability and abnormal serum thyroid hormone levels were screened using whole\u2010exome sequencing (WES). We collected patients\u2032 clinical data and assessed their cognitive, linguistic, and motor abilities. Candidate variants were verified by Sanger sequencing, and their pathogenicity and evolutionary conservation were analyzed using in silico prediction tools. Protein expression and subcellular localization of mutant MCT8 were evaluated by Western blotting and immunofluorescence microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Exome sequencing identified seven previously uncharacterized\n                      <jats:italic>SLC16A2<\/jats:italic>\n                      variants in 10 unrelated male patients (nine families). These included three missense mutations (p.Ala150Thr,p.Gly208Arg, and p.Gly208Asp), three frameshift mutations (p.Leu168fs, p.Ser243Cysfs, and p.Val485fs), one deletion\u2013insertion mutation (p.Ile328_Ala329delinsThr), and one balanced translocation, t(X,12) (q13.2; q13.13). All patients exhibited global developmental delay, axial hypotonia, dystonia, and abnormal thyroid hormone profiles. In vitro experiments demonstrated significantly reduced expression of mutant proteins compared with the wild\u2010type. Immunofluorescence showed that, in addition to residual plasma membrane localization, mutant proteins were also partially retained in the cytoplasm, whereas the wild\u2010type protein localized exclusively to the plasma membrane.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings expand the genotypic and phenotypic spectrum of MCT8 deficiency. The results suggest that\n                      <jats:italic>SLC16A2<\/jats:italic>\n                      variants lead to a loss of function through decreased protein expression and defective plasma membrane trafficking.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/3319748","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:27:27Z","timestamp":1778941647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Variants in the SLC16A2 Gene Associated With Allan\u2013Herndon\u2013Dudley Syndrome in China"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7982-0033","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijia","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoli","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2874-6207","authenticated-orcid":false,"given":"Xiaoqin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0094-2099","authenticated-orcid":false,"given":"Min","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300909200"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnz008"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17226-7"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaf311"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-023-00481-w"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0306"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2021.100901"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa795"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00082"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2302325120"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1061"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14332"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.12.003"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30153-4"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25168585"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.1050023"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab750"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S379703"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30155-X"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106195"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.04.002"}],"container-title":["Human 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