{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:19:03Z","timestamp":1790695143439,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Microcephaly is a rare neurodevelopmental disorder characterized by reduced skull circumference and brain volume that occurs sporadically in farm animals. We investigated an early\u2010onset neurodegenerative disorder observed in seven lambs of purebred Kerry Hill sheep. Clinical signs included inability to stand or severe ataxia, convulsions, and early death. Diagnostic imaging and brain necropsy confirmed microcephaly. The pedigree of the lambs suggested monogenic autosomal recessive inheritance. We sequenced the genome of one affected lamb, and comparison with 115 control genomes revealed a single private protein\u2010changing variant. This frameshift variant, <jats:italic>MFSD2A<\/jats:italic>: c.285dupA, p.(Asp96fs*9), represents a 1\u2010bp duplication predicted to truncate 80% of the open reading frame. MFSD2A is a transmembrane protein that is essential for maintaining blood\u2013brain barrier homeostasis and plays a key role in regulating brain lipogenesis. Human <jats:italic>MFSD2A<\/jats:italic> pathogenic variants are associated with a neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA, OMIM 616486). Here we present evidence for the occurrence of a recessively inherited form of microcephaly in sheep due to a loss\u2010of\u2010function variant in <jats:italic>MFSD2A<\/jats:italic> (OMIA 002371\u20109940). To the best of our knowledge, this is the first report of a spontaneous <jats:italic>MFSD2A<\/jats:italic> variant in domestic animals.<\/jats:p>","DOI":"10.1111\/age.13374","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T11:14:54Z","timestamp":1699010094000},"page":"152-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>MFSD2A<\/i> frameshift variant in Kerry Hill sheep with microcephaly"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7043-3117","authenticated-orcid":false,"given":"Gabriela","family":"Rudd\u00a0Garces","sequence":"first","affiliation":[{"name":"Institute of Animal Breeding and Genetics Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6521-1285","authenticated-orcid":false,"given":"Anna","family":"Letko","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene M.","family":"H\u00e4fliger","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3600-2019","authenticated-orcid":false,"given":"Jana","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Veterinary Pathology Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1858-2267","authenticated-orcid":false,"given":"Christiane","family":"Herden","sequence":"additional","affiliation":[{"name":"Institute for Veterinary Pathology Justus Liebig University Giessen  Giessen Germany"},{"name":"Center for Mind, Brain and Behavior Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Nesseler","sequence":"additional","affiliation":[{"name":"Landeslabor Hessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Wagner","sequence":"additional","affiliation":[{"name":"Veterinary Clinic for Reproduction and Neonatology Justus Liebig University  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Clinic for Small Animals, Neurosurgery, Neuroradiology and Clinical Neurology Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-522X","authenticated-orcid":false,"given":"Cord","family":"Dr\u00f6gem\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2032-0840","authenticated-orcid":false,"given":"Gesine","family":"L\u00fchken","sequence":"additional","affiliation":[{"name":"Institute of Animal Breeding and Genetics Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3313"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13324"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-7020-5317-7.00004-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2006443"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006997"},{"key":"e_1_2_7_7_1","unstructured":"Daetwyler H. Kijas J. McWilliam S. Clarke S.&Brauning R.(2019)Sheep genome variants V2. Commonwealth Scientific and Industrial Research Organisation (CSIRO). 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