{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:48:23Z","timestamp":1789728503355,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,5]],"date-time":"2020-01-05T00:00:00Z","timestamp":1578182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011410","name":"School of Medicine, University of South Carolina","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The rare, X\u2010linked neurodegenerative disorder, Mohr\u2013Tranebjaerg syndrome (also called deafness\u2010dystonia\u2010optic neuronopathy [DDON] syndrome), is caused by mutations in the\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      gene. DDON syndrome is characterized by dystonia, early\u2010onset deafness, and various other neurological manifestations. The\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      gene product localizes to the intermembrane space in mitochondria where it functions in the import of nuclear\u2010encoded proteins into the mitochondrial inner membrane. Frameshifts or premature stops represent the majority of mutations in\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      that cause DDON syndrome. However, missense mutations have also been reported that result in loss of the\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      gene product.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We report a novel\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      variant in a patient with DDON syndrome that alters the initiation codon and employed functional analyses to determine the significance of the variant and its impact on mitochondrial morphology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The novel base change in the\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      gene (c.1A&gt;T, p.Met1Leu) results in no detectable protein and a reduction in\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      transcript abundance. We observed a commensurate decrease in the steady\u2010state level of the Tim13 protein (the binding partner of Tim8a) but no decrease in\n                      <jats:italic>TIMM13<\/jats:italic>\n                      transcripts. Patient fibroblasts exhibited elongation and\/or increased fusion of mitochondria, consistent with prior reports.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case expands the spectrum of mutations that cause DDON syndrome and demonstrates effects on mitochondrial morphology that are consistent with prior reports.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1121","type":"journal-article","created":{"date-parts":[[2020,1,5]],"date-time":"2020-01-05T23:10:11Z","timestamp":1578265811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Functional analysis of a novel mutation in the\n                    <i>TIMM8A<\/i>\n                    gene that causes deafness\u2010dystonia\u2010optic neuronopathy syndrome"],"prefix":"10.1002","volume":"8","author":[{"given":"Addison","family":"Neighbors","sequence":"first","affiliation":[{"name":"Greenwood Genetic Center Greenwood SC USA"},{"name":"University of South Carolina School of Medicine Columbia SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonya","family":"Moss","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Holloway","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok\u2010Ho","family":"Yu","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran","family":"Annese","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Skinner","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Saneto","sequence":"additional","affiliation":[{"name":"Program for Mitochondrial Medicine and Metabolism Division of Pediatric Neurology Neuroscience Institute Seattle's Children's Hospital University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0975-4963","authenticated-orcid":false,"given":"Richard","family":"Steet","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31079"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.10.041"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e3180581944"},{"key":"e_1_2_7_5_1","first-page":"122","article-title":"Genetic diagnosis as a tool for personalized treatment of Duchenne muscular dystrophy","volume":"35","author":"Bello L.","year":"2016","journal-title":"Acta Myologica: Myopathies and Cardiomyopathies"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.07.069"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg174"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-007-8000-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.026"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm079"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr458"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402107"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25033"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914387107"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201154200"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-177"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201110034"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.48828"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153527"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25394"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.647"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200107000-00017"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12210"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh217"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105313200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200923030-00003"},{"key":"e_1_2_7_27_1","volume-title":"GeneReviews(R)","author":"Tranebjaerg L.","year":"1993"},{"key":"e_1_2_7_28_1","first-page":"337","volume-title":"Mitochondrial disorders caused by nuclear genes","author":"Tranebjaerg L.","year":"2012"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1076\/opge.22.4.207.2220"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.4.257"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.6.1004"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-018-0741-3"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2010.11.002"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq007"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.1121","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1121","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1121","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T05:55:04Z","timestamp":1708494904000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,5]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/mgg3.1121"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1121","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,5]]},"assertion":[{"value":"2019-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1121"}}