{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:34:47Z","timestamp":1774596887974,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>LONP1<\/jats:italic>\n                      encodes an ATP-dependent protease essential for maintaining mitochondrial homeostasis.\n                      <jats:italic>LONP1<\/jats:italic>\n                      variants have been associated with cerebral-ocular-dental-auricular-skeletal anomalies syndrome, pediatric cataract, congenital diaphragmatic hernia, and neurodevelopmental disorders; moreover, these variants can be inherited in both autosomal recessive and autosomal dominant modes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective analysis of the clinical data and genetic test results of a Chinese boy diagnosed as having mitochondrial encephalopathy. Subsequently, we evaluated the pathogenicity of candidate variants and conducted a literature review encompassing 47 cases of\n                      <jats:italic>LONP1<\/jats:italic>\n                      variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      The proband was a 4.5-year-old boy who had experienced focal epilepsy seizures since birth. He presented with recurrent seizures and did not respond to anti-seizure medications. He showed global developmental delay, microcephaly, pachygyria, and hyperlactatemia. Initial genetic testing through single and trio whole-exome sequencing before 6 months of age yielded no conclusive results. Recurrent seizures and elevated lactic acid levels at 18 months of age prompted reanalysis with trio whole-exome sequencing, leading to the identification of a likely pathogenic variant in\n                      <jats:italic>LONP1<\/jats:italic>\n                      : c.901C&amp;gt;T (p.Arg301Trp). By 10 months of age, the patient had already developed primary adrenal insufficiency and experienced multiple adrenal crises triggered by respiratory infections, necessitating admission to the intensive care unit. The crises were effectively managed with hydrocortisone. However, despite intensive medical interventions, the patient succumbed to a metabolic crisis triggered by a severe respiratory infection at the age of 4.5 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In this study, we discuss the clinical manifestations and genetic features of a pediatric patient with mitochondrial encephalopathy resulting from a rare\n                      <jats:italic>LONP1<\/jats:italic>\n                      variant, emphasizing the diagnostic and therapeutic challenges of mitochondrial disorders. Furthermore, our findings enhance the understanding of\n                      <jats:italic>LONP1<\/jats:italic>\n                      -related diseases and offer additional evidence supporting the autosomal dominant inheritance pattern of\n                      <jats:italic>LONP1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1779332","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:37:24Z","timestamp":1774593444000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the genome: clinical challenges in diagnosing LONP1-related mitochondrial disorders"],"prefix":"10.3389","volume":"14","author":[{"given":"Qianni","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurology, Shenzhen Children\u2019s Hospital","place":["Shenzhen, China"]},{"name":"Shenzhen Pediatrics Institute of Shantou University Medical College","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Children\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Be Creative Lab Co., Ltd.","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Children\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Children\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Children\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dezhi","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Children\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianxiang","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Children\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shenzhen Children\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.mito.2020.01.004","article-title":"LONP1 de novo dominant mutation causes mitochondrial encephalopathy with loss of LONP1 chaperone activity and excessive LONP1 proteolytic activity","volume":"51","author":"Besse","year":"2020","journal-title":"Mitochondrion"},{"key":"B2","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1210\/jc.2015-1710","article-title":"Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline","volume":"101","author":"Bornstein","year":"2016","journal-title":"J. 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