{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:24:40Z","timestamp":1792193080872,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/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\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["21Y21901000"],"award-info":[{"award-number":["21Y21901000"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["24Y12800700"],"award-info":[{"award-number":["24Y12800700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Kallmann syndrome (KS) is a genetic disorder characterized by impaired reproductive system and olfactory development. This study aimed to identify a novel variant of\n SEMA3A<\/jats:italic>\n in a KS patient and explore its potential pathogenic mechanism.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A gene panel was used to identify potential pathogenic mutations. Wild\u2010type and mutant\n SEMA3A<\/jats:italic>\n overexpression plasmids were constructed. Western blotting, RNA sequencing, and cell migration were performed to assess the effects of\n SEMA3A<\/jats:italic>\n gene variations on GnRH neuronal migration.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A novel heterozygous mutation in the\n SEMA3A<\/jats:italic>\n gene (NM_006080.3: exon 6\u20139 deletion) was identified in the proband, as well as in his father and sister. The spatial structure of the\n SEMA3A<\/jats:italic>\n mutant protein was relatively looser. In\u00a0vitro experiments revealed that\n SEMA3A<\/jats:italic>\n mutation reduced SEMA3A expression and inhibited GnRH neuronal migration. RNAseq analysis revealed that the expression of 76 genes was upregulated and that of 104 genes was downregulated after\n SEMA3A<\/jats:italic>\n mutation. The altered gene clusters were enriched mainly in cell migration, male gonad development, motor proteins, and neuron synapses.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In this study, we identified a novel variant of\n SEMA3A<\/jats:italic>\n in a KS patient and verified its function. These findings expand the mutation spectrum of the\n SEMA3A<\/jats:italic>\n gene and offer a theoretical basis for the clinical diagnosis of KS.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70190","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T10:18:47Z","timestamp":1768385927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification and Functional Characterization of a Novel\n SEMA3A<\/scp>\n Exon Deletion Variant in Kallmann Syndrome"],"prefix":"10.1002","volume":"14","author":[{"given":"Shaolian","family":"Zang","sequence":"first","affiliation":[{"name":"Research Center for Clinical Diagnosis and Treatment of Sexual Development Disorders, Shanghai Children's Hospital, School of Medicine Shanghai Jiao Tong University Shanghai 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