{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:05:00Z","timestamp":1789772700572,"version":"4.0.1"},"reference-count":26,"publisher":"BMJ","issue":"7","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071409"],"award-info":[{"award-number":["82071409"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171846"],"award-info":[{"award-number":["82171846"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U20A20356"],"award-info":[{"award-number":["U20A20356"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["20220484017"],"award-info":[{"award-number":["20220484017"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["20230484403"],"award-info":[{"award-number":["20230484403"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,2,7]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Congenital myopathies are a clinical, histopathological and genetic heterogeneous group of inherited muscle disorders that are defined on peculiar architectural abnormalities in the muscle fibres. Although there have been at least 33 different genetic causes of the disease, a significant percentage of congenital myopathies remain genetically unresolved. The present study aimed to report a novel\n                      <jats:italic>TUBA4A<\/jats:italic>\n                      variant in two unrelated Chinese patients with sporadic congenital myopathy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A comprehensive strategy combining laser capture microdissection, proteomics and whole-exome sequencing was performed to identify the candidate genes. In addition, the available clinical data, myopathological changes, the findings of electrophysiological examinations and thigh muscle MRIs were also reviewed. A cellular model was established to assess the pathogenicity of the\n                      <jats:italic>TUBA4A<\/jats:italic>\n                      variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a recurrent novel heterozygous de novo c.679C&gt;T (p.L227F) variant in the\n                      <jats:italic>TUBA4A<\/jats:italic>\n                      (NM_006000), encoding tubulin alpha-4A, in two unrelated patients with clinicopathologically diagnosed sporadic congenital myopathy. The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiquitin-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of the L227F mutant TUBA4A resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings expanded the phenotypic and genetic manifestations of\n                      <jats:italic>TUBA4A<\/jats:italic>\n                      as well as tubulinopathies, and added a new type of congenital myopathy to be taken into consideration in the differential diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2023-109786","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T13:20:44Z","timestamp":1709040044000},"page":"626-632","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Novel\n                    <i>TUBA4A<\/i>\n                    variant causes congenital myopathy with focal myofibrillar disorganisation"],"prefix":"10.1136","volume":"61","author":[{"given":"Yalan","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Neurology, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingzhi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hunan Children's Hospital, 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