{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T23:22:19Z","timestamp":1784330539653,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T00:00:00Z","timestamp":1603152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R00GM11421"],"award-info":[{"award-number":["R00GM11421"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Glomerulopathies affect kidney glomeruli and can lead to end\u2010stage renal disease if untreated. Clinical and experimental evidence have identified numerous (&gt;20) genetic mutations in the mitochondrial coenzyme Q8B protein (<jats:italic>COQ8B<\/jats:italic>) primarily associated with nephrotic syndrome. Yet, little else is understood about COQ8B activity in renal pathogenesis and its role in mitochondrial dysfunction. We identified additional novel <jats:italic>COQ8B<\/jats:italic> mutations in a glomerulopathy patient and aimed to define the potential structural and functional defects of <jats:italic>COQ8B<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, Participants, and Measurements<\/jats:title><jats:p>Whole exome sequencing was performed on a Hispanic female presenting with proteinuria. Novel mutations in the <jats:italic>COQ8B<\/jats:italic> gene were identified. The effects of mutation on protein function, mitochondrial morphology, and disease progression were investigated by histopathology, transmission electron microscopy, homology modeling, and in silico structural analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We have characterized the pathophysiology of novel <jats:italic>COQ8B<\/jats:italic> mutations, compound heterozygous for two alterations c.1037T&gt;G (p.I346S), and c.1560G&gt;A (p.W520X), in the progression of proteinuria in a Hispanic female. Histopathology revealed defects in podocyte structure and mitochondrial morphology. In silico and computation analyses highlight possible structural origins of COQ8B dysfunction in the presence of mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Novel mutations in <jats:italic>COQ8B<\/jats:italic> present promising biomarkers for the early detection and therapeutic targeting of mitochondrial glomerulopathy. Insights from structural modeling suggest roles of mutation\u2010dependent alterations in COQ8B allosteric regulation, protein folding, or stability in renal pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.61909","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T06:49:35Z","timestamp":1603262975000},"page":"60-67","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The role of novel <scp><i>COQ8B<\/i><\/scp> mutations in glomerulopathy and related kidney defects"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5093-3405","authenticated-orcid":false,"given":"Asmaa S.","family":"AbuMaziad","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Nephrology University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarjani M.","family":"Thaker","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Tomasiak","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chyi Chyi","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen K.","family":"Galindo","sequence":"additional","affiliation":[{"name":"Center for Applied Genetics and Genomic Medicine and Department of Pediatrics University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Eugene","family":"Hoyme","sequence":"additional","affiliation":[{"name":"Center for Applied Genetics and Genomic Medicine and Department of Pediatrics University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69000"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-017-3634-3"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200300771"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9749-9"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv332"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.214"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2018.07.008"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2017.892"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12328-019-00937-3"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050017"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja505017f"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014121240"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-017-0392-9"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1310"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-017-3657-9"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm017"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.5"},{"key":"e_1_2_10_19_1","unstructured":"SchrodingerLLC.2015. 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