{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:49:06Z","timestamp":1792712946996,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants of\n                      <jats:italic>IBA57<\/jats:italic>\n                      (OMIM ID: 615330) are usually associated with multiple mitochondrial dysfunction syndrome (MMDS) and hereditary spastic paraplegia type 74 (SPG74). Here, we present a novel compound heterozygous\n                      <jats:italic>IBA57<\/jats:italic>\n                      mutation in a boy with severe global developmental delay, optic atrophy, spastic paraplegia, and focal epileptic seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The clinical data of a child diagnosed with MMDS were retrospectively collected. Video electroencephalogram (VEEG), cranial magnetic resonance imaging (MRI), and family whole\u2010exome sequencing (WES) were performed. Suspected mutation sites were further confirmed using Sanger sequencing. The activities of mitochondrial respiratory chain complexes I\u2013IV were determined in peripheral blood mononuclear cells. The phylogenetic conservation of the affected residues was assessed by multiple sequence alignment of\n                      <jats:italic>IBA57<\/jats:italic>\n                      gene orthologs. Furthermore, we conducted a review of the relevant literature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Whole\u2010exome sequencing identified compound heterozygous variants in the\n                      <jats:italic>IBA57<\/jats:italic>\n                      gene: c.395_400dup (p.V132_Q133dup) and c.832delC (p.R278Afs*23), inherited from his phenotypically normal father and mother, respectively. Biochemical assays demonstrated selective reduction of complexes\u2009I and\u2009II activities, with normal complexes III and IV, consistent with impaired 4Fe\u20134S cluster maturation. Phylogenetic alignment revealed strict conservation of residues V132\u2013Q133 and R278 across vertebrates. These variants had not been previously reported in domestic or international databases. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the former was classified as a variant of uncertain significance (PM4\u2009+\u2009PM2), while the latter was classified as likely pathogenic (PVS1\u2009+\u2009PM2).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Diseases associated with\n                      <jats:italic>IBA57<\/jats:italic>\n                      gene variants are autosomal recessive disorders with a broad clinical phenotypic spectrum. Early genetic testing and family screening are beneficial for the diagnosis, treatment, and prognosis of the disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70200","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:47:48Z","timestamp":1768967268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multiple Mitochondrial Dysfunction Syndrome Caused by\n                    <scp>\n                      <i>IBA57<\/i>\n                    <\/scp>\n                    Gene Mutation: A Case Report and Literature Review"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6472-4205","authenticated-orcid":false,"given":"Jia","family":"Xu","sequence":"first","affiliation":[{"name":"Linyi People's Hospital Affiliated to Shandong Second Medical University  Linyi China"},{"name":"Department of Pediatric Neurology Linyi People's Hospital  Linyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Linyi People's Hospital Affiliated to Shandong Second Medical University  Linyi China"},{"name":"Department of Pediatric Neurology Linyi People's Hospital  Linyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Linyi People's Hospital  Linyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-3187","authenticated-orcid":false,"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Linyi People's Hospital  Linyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyu","family":"Shi","sequence":"additional","affiliation":[{"name":"Linyi People's Hospital Affiliated to Shandong Second Medical University  Linyi China"},{"name":"Department of Pediatric Neurology Linyi People's Hospital  Linyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Linyi People's Hospital Affiliated to Shandong Second Medical University  Linyi China"},{"name":"Department of Pediatric Neurology Linyi People's Hospital  Linyi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt107"},{"issue":"24","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1212\/WNL.0000000000200671","article-title":"Teaching Neuroimage: IBA57 Mutation\u2010Associated Infantile Cavitating Leukoencephalopathy","volume":"98","author":"Ajith C.","year":"2022","journal-title":"Neurology"},{"issue":"5","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1212\/NXG.0000000000000184","article-title":"IBA57 Mutations Abrogate Iron\u2010Sulfur Cluster Assembly Leading to Cavitating Leukoencephalopathy","volume":"3","author":"Akihiko I.","year":"2017","journal-title":"Neurology. 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