{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T04:19:36Z","timestamp":1769833176434,"version":"3.49.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>\n                    The diagnosis of Sengers syndrome, a rare mitochondrial disorder, is often challenged by phenotypic mimicry. We report a diagnostically instructive case of a 4-month-old female who presented with the classic triad of congenital cataracts, hypertrophic cardiomyopathy, and lactic acidosis. Initial whole-exome sequencing (WES) was confounded by the finding of a heterozygous variant in\n                    <jats:italic>CRYBA2<\/jats:italic>\n                    and only a single heterozygous nonsense mutation in\n                    <jats:italic>AGK<\/jats:italic>\n                    (c.409C&amp;gt;T, p.Arg137*). The persistence of a multisystemic phenotype inconsistent with an isolated cataract disorder prompted further investigation. Copy number variation (CNV) analysis of the WES data revealed a large heterozygous deletion in\n                    <jats:italic>AGK<\/jats:italic>\n                    , which breakpoint-specific polymerase chain reaction and Sanger sequencing precisely characterized as a novel 7.6\u2005kb deletion (chr7:141297542-141305156). This confirmed compound heterozygosity, yielding a definitive diagnosis of Sengers syndrome and reclassifying the\n                    <jats:italic>CRYBA2<\/jats:italic>\n                    variant as incidental. Crucially, breakpoint analysis indicated a non-Alu-mediated mechanism for the deletion. This case highlights the critical importance of CNV analysis in resolving genetically ambiguous autosomal recessive cases and provides novel insight into the structural mutational landscape of\n                    <jats:italic>AGK<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fped.2026.1714952","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:39:09Z","timestamp":1769783949000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Sengers syndrome caused by a novel 7.6\u2005kb AGK deletion misdiagnosed as isolated congenital cataract"],"prefix":"10.3389","volume":"14","author":[{"given":"Xingwang","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Hainan Clinical Medical Center, Hainan Academician Team Innovation Center","place":["Haikou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"107626","DOI":"10.1016\/j.ymgme.2023.107626","article-title":"Sengers syndrome and AGK-related disorders \u2013 mini review of phenotypic and clinical outcomes in molecularly confirmed cases","volume":"139","author":"Wu","year":"2023","journal-title":"Mol Genet Metab"},{"key":"B2","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/S0022-3476(75)80217-4","article-title":"Congenital cataract and mitochondrial myopathy of skeletal and heart muscle associated with lactic acidosis after exercise","volume":"86","author":"Sengers","year":"1975","journal-title":"J Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"148726","DOI":"10.1016\/j.gene.2024.148726","article-title":"A novel base substitution mutation of the CRYBA2 gene is associated with autosomal dominant congenital cataract","volume":"927","author":"Liu","year":"2024","journal-title":"Gene"},{"key":"B4","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.ajhg.2011.12.005","article-title":"Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome","volume":"90","author":"Mayr","year":"2012","journal-title":"Am J Hum Genet"},{"key":"B5","first-page":"683","article-title":"A novel AGK splicing mutation in a patient with Sengers syndrome and left ventricular non-compaction cardiomyopathy","volume":"94","author":"Fan","year":"2023","journal-title":"Pediatr Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/15513815.2019.1639089","article-title":"Atypical presentation of Sengers syndrome: a novel mutation revealed with postmortem genetic testing","volume":"39","author":"Guleray","year":"2020","journal-title":"Fetal Pediatr Pathol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"639687","DOI":"10.3389\/fped.2021.639687","article-title":"Case report: two Chinese infants of Sengers syndrome caused by mutations in AGK gene","volume":"9","author":"Wang","year":"2021","journal-title":"Front Pediatr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1007\/s11011-017-0101-6","article-title":"Mutation in the AGK gene in two siblings with unusual Sengers syndrome","volume":"32","author":"Allali","year":"2017","journal-title":"Metab Brain Dis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1146\/annurev-genom-121222-120601","article-title":"Copy number variants: deletion and duplication syndromes","volume":"26","author":"Harner","year":"2025","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1146\/annurev-cellbio-111822-014426","article-title":"Microhomology-mediated end-joining chronicles: tracing the evolutionary footprints of genome protection","volume":"40","author":"Sfeir","year":"2024","journal-title":"Annu Rev Cell Dev Biol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1714952\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:39:11Z","timestamp":1769783951000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1714952\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":10,"alternative-id":["10.3389\/fped.2026.1714952"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1714952","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"article-number":"1714952"}}