{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T13:11:16Z","timestamp":1762348276230,"version":"build-2065373602"},"reference-count":37,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["No. 2022YFC2703100"],"award-info":[{"award-number":["No. 2022YFC2703100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing Natural Science Foundation","award":["No. 7224327 and No. 7234364"],"award-info":[{"award-number":["No. 7224327 and No. 7234364"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82173084, No.82171393 and No.82471430"],"award-info":[{"award-number":["No. 82173084, No.82171393 and No.82471430"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Basic-Clinical Laboratory of Pediatric Epilepsy and Cognitive Developmental","award":["No. 3-1-013-03"],"award-info":[{"award-number":["No. 3-1-013-03"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">B3GALNT2<\/jats:italic>\n                      mutations cause \u03b1-dystroglycanopathy (\u03b1-DGP), a rare condition characterized by muscular dystrophy, brain malformations, and developmental delay. However, its pathogenic mechanisms remain poorly understood. To date, limited cases have been reported, and the pathogenic mechanisms remain incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Clinical and genetic data from 3 newly diagnosed Chinese patients and 28 patients previously diagnosed with\n                      <jats:italic toggle=\"yes\">B3GALNT2<\/jats:italic>\n                      -related \u03b1-DGP were analyzed. Using patient-derived fibroblasts, \u03b1-dystroglycan (\u03b1-DG) glycosylation and laminin-binding capacity were assessed by immunoblotting, laminin overlay and immunofluorescence.\n                      <jats:italic toggle=\"yes\">B3GALNT2<\/jats:italic>\n                      mRNA and protein levels were quantified by real-time PCR and immunoblotting. Enzymatic activity was measured using purified recombinant\n                      <jats:italic toggle=\"yes\">B3GALNT2<\/jats:italic>\n                      proteins. Differentially expressed genes were identified via an mRNA microarray.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All three patients carried compound heterozygous variants involving one truncating and one missense mutation. Two novel mutations (c.657_658insTT and c.1384T\u2009&gt;\u2009C) were identified. Functional studies confirmed that the missense mutations (Y436C and C462R) impaired enzymatic activity to 40\u201350% of wild-type levels, while splice variants caused frameshifts and likely complete loss of protein. Despite partial residual activity, all patients showed severely reduced \u03b1-DG glycosylation and loss of laminin binding, consistent with a functional threshold effect. Transcriptomic analysis revealed upregulation of\n                      <jats:italic toggle=\"yes\">CHST10<\/jats:italic>\n                      in two patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study expands the mutational spectrum of\n                      <jats:italic toggle=\"yes\">B3GALNT2<\/jats:italic>\n                      -related \u03b1-DGP and provides mechanistic insight into the pathogenicity of novel variants. Our findings support a functional threshold model for B3GALNT2 activity in \u03b1-DG glycosylation and suggest CHST10 as a potential transcriptional responder to glycosylation defects. These results deepen the understanding of\n                      <jats:italic toggle=\"yes\">B3GALNT2<\/jats:italic>\n                      -related dystroglycanopathies and may inform future diagnostic and therapeutic strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/22143602251360270","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T06:47:25Z","timestamp":1752648445000},"page":"814-827","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathogenic mechanisms and clinical insights into\n                    <i>B3GALNT2<\/i>\n                    -related alpha-dystroglycanopathies"],"prefix":"10.1177","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-3386","authenticated-orcid":false,"given":"Xiaona","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Children's Hospital, 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