{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T10:07:13Z","timestamp":1778494033199,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    Lissencephaly and cerebellar hypoplasia (LCH) represents a spectrum of congenital developmental malformations of the cerebral cortex and cerebellum, mostly occurring as inherited conditions caused by variants in an increasingly recognized number of genes. LCH has been identified in three Dorset-cross lambs with congenital neurological signs in Australia. Lambs were unable to walk and had reduced vision, and one lamb developed a hypermetric gait and intention tremors. Grossly, the lambs had diffuse pachygyria with reduction in white matter, mild bilateral ventriculomegaly of the lateral ventricles, and a markedly hypoplastic cerebellum. Histologically, there was disorganization of neurons within the cerebral cortex and hippocampus. The cerebellar vermis had disorganized, thin, and hypocellular gray matter with frequent ectopic Purkinje cells, while identifiable folia were largely absent within the hemispheres. Luxol fast blue stain and glial fibrillary acidic protein, neuronal nuclear protein, synaptophysin, and neuron-specific enolase immunohistochemistry confirmed the thickened, disorganized cerebral cortical gray matter and reduced white matter. Within the cerebellum, immunohistochemistry demonstrated marked dysplasia. Whole-genome sequencing analysis and prediction of variant effects identified a missense variant of interest in the candidate gene\n                    <jats:italic toggle=\"yes\">reelin<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">RELN<\/jats:italic>\n                    ; NC_040255.1:g.50288685C&gt;T; NM_001306121.1:c.7088G&gt;A; NP_001293050.1:p.(R2363H)) with a deleterious Sorting Intolerant from Tolerant (SIFT) score. Sanger sequencing identified that the variant segregated with LCH disease in the 3 affected individuals, their sire, and 6 unaffected flock members. The NP_001293050.1: p.(R2363H) substitution is predicted to decrease the stability of the protein (\u0394\u0394G = \u22121.55 kcal\/mol). Pathological and genetic findings are consistent with previously described phenotypes of\n                    <jats:italic toggle=\"yes\">RELN<\/jats:italic>\n                    variants in Churra sheep, dogs, and humans.\n                  <\/jats:p>","DOI":"10.1177\/03009858241283501","type":"journal-article","created":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T06:32:08Z","timestamp":1728714728000},"page":"522-531","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel missense variant in the\n                    <i>RELN<\/i>\n                    gene in sheep with lissencephaly and cerebellar hypoplasia"],"prefix":"10.1177","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1609-4772","authenticated-orcid":false,"given":"Leah K.","family":"Manning","sequence":"first","affiliation":[{"name":"Elizabeth Macarthur Agricultural Institute, NSW Department of Primary Industries and Regional Development, Menangle, NSW, Australia"},{"name":"The University of Sydney, Camden, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Winkenwerder","sequence":"additional","affiliation":[{"name":"Elizabeth Macarthur Agricultural Institute, NSW Department of Primary Industries and Regional Development, Menangle, NSW, Australia"},{"name":"The University of Sydney, Camden, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Baskind","sequence":"additional","affiliation":[{"name":"South East Local Land Services, Braidwood, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie L. M.","family":"Eager","sequence":"additional","affiliation":[{"name":"Elizabeth Macarthur Agricultural Institute, NSW Department of Primary Industries and Regional Development, Menangle, NSW, Australia"},{"name":"The University of Sydney, Camden, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8449-1502","authenticated-orcid":false,"given":"Cali E.","family":"Willet","sequence":"additional","affiliation":[{"name":"The University of Sydney, Camperdown, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Porebski","sequence":"additional","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6959-9398","authenticated-orcid":false,"given":"Brendon A.","family":"O\u2019Rourke","sequence":"additional","affiliation":[{"name":"Elizabeth Macarthur Agricultural Institute, NSW Department of Primary Industries and Regional Development, Menangle, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imke","family":"Tammen","sequence":"additional","affiliation":[{"name":"The University of Sydney, Camden, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Gimeno","sequence":"additional","affiliation":[{"name":"Elizabeth Macarthur Agricultural Institute, NSW Department of Primary Industries and Regional Development, Menangle, NSW, Australia"},{"name":"The University of Sydney, Camden, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-6026","authenticated-orcid":false,"given":"Pedro","family":"Pinczowski","sequence":"additional","affiliation":[{"name":"Elizabeth Macarthur Agricultural Institute, NSW Department of Primary Industries and Regional Development, Menangle, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,10,12]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Andrews S. 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