{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:05:17Z","timestamp":1790168717290,"version":"4.1.0"},"reference-count":10,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25K19225"],"award-info":[{"award-number":["JP25K19225"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109760"],"award-info":[{"award-number":["JP24ek0109760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109617"],"award-info":[{"award-number":["JP24ek0109617"]}],"id":[{"id":"10.13039\/100009619","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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Biallelic variants in\n                      <jats:italic>VPS41<\/jats:italic>\n                      , encoding a subunit of the HOPS complex, cause autosomal recessive spinocerebellar ataxia 29 (SCAR29), a rare neurodevelopmental disorder with an incompletely defined phenotypic and molecular spectrum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated a 24\u2010year\u2010old man with cerebellar ataxia, hypotonia, and intellectual disability. Exome sequencing identified four candidate\n                      <jats:italic>VPS41<\/jats:italic>\n                      variants. Because maternal DNA was unavailable, long\u2010read genome sequencing was performed to determine allelic configuration, followed by RNA and protein analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In addition to typical SCAR29 features, the patient showed previously unreported findings, including swan\u2010neck deformities and pes cavus. Long\u2010read genome sequencing demonstrated that two\n                      <jats:italic>VPS41<\/jats:italic>\n                      variants were in trans. RNA analysis revealed distinct splicing consequences: one allele produced an out\u2010of\u2010frame transcript predicted to undergo nonsense\u2010mediated decay, whereas the other generated an in\u2010frame exon\u2010skipped transcript. These complementary defects reduced\n                      <jats:italic>VPS41<\/jats:italic>\n                      expression at both transcript and protein levels, supporting pathogenicity and variant reclassification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings expand the phenotypic spectrum of\n                      <jats:italic>VPS41<\/jats:italic>\n                      \u2010related disease and highlight the value of long\u2010read allelic resolution in clarifying pathogenic mechanisms in rare genetic disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70285","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:19:00Z","timestamp":1787818740000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic\n                    <scp>\n                      <i>VPS41<\/i>\n                    <\/scp>\n                    Variants in Autosomal Recessive Spinocerebellar Ataxia 29 Resolved by Long\u2010Read Sequencing and\n                    <scp>RNA<\/scp>\n                    Analysis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2024-4790","authenticated-orcid":false,"given":"Natsuki","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Pediatrics Central Hospital, Aichi Developmental Disability Center  Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-7491","authenticated-orcid":false,"given":"Yosuke","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Genetics, Research Institute of Environmental Medicine (RIeM) Nagoya University  Nagoya Japan"},{"name":"Department of Human Genetics and Molecular Biology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Medical Genomics Center Nagoya University Hospital  Nagoya Japan"},{"name":"Department of Pediatrics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-0875","authenticated-orcid":false,"given":"Hiromi","family":"Nyuzuki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Niigata University Medical and Dental Hospital  Niigata 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