{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:24:53Z","timestamp":1784805893887,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"2-3","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"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":["Annals of Human Genetics"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Combined oxidative phosphorylation (OXPHOS) deficiency 44 (COXPD44; MIM# 618855) is caused by biallelic pathogenic variants in FAS\u2010activated serine\u2013threonine kinase domain 2 (\n                      <jats:italic>FASTKD2)<\/jats:italic>\n                      (MIM# 612322). COXPD44 is characterized by variable clinical features\u2014developmental delay, chronic epileptic encephalopathy, seizure disorder\/status epilepticus and cerebellar ataxia. We ascertained one sib\u00a0with episodic acute encephalomyopathy triggered by acute gastroenteritis and associated with haematological abnormalities, rhabdomyolysis leading to acute kidney injury, hypotensive shock leading to early death and a similarly affected sib with early death. Both siblings were normal neurologically in between the acute episodes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>Whole exome sequencing (WES) was performed in the elder sibling. Mitochondrial respiratory chain enzyme activity assaywas performed in fibroblast cells and muscle tissue of the elder sibling. Also, Adenosine triphosphate (ATP) determination assay was done in fibroblast cells of the elder sibling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WES revealed compound heterozygous missense likely pathogenic variants in\n                      <jats:italic>FASTKD2<\/jats:italic>\n                      . Mitochondrial respiratory chain enzyme activity in muscle tissue showed reduced complex IV activity and ATP determination assay showed a reduction of ATP in skin fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Herein, we report two siblings with novel clinical phenotype associated with COXPD44. Our report further validates the biallelic variants in\n                      <jats:italic>FASTKD2<\/jats:italic>\n                      associated with the variable phenotypes and mitochondrial OXPHOS defect.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.12585","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T07:59:37Z","timestamp":1732262377000},"page":"77-88","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intermittent episodes of acute severe encephalomyopathy and early death in two siblings caused by biallelic likely pathogenic variants in\n                    <i>FASTKD2<\/i>\n                    : Expanding phenotype and literature review"],"prefix":"10.1111","volume":"89","author":[{"given":"Namanpreet","family":"Kaur","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of, Higher Education  Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puneeth H.","family":"Somashekar","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of, Higher Education  Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sekar","family":"Deepha","sequence":"additional","affiliation":[{"name":"Neuromuscular laboratory, Department of Neuropathology National Institute of Mental Health and Neurosciences (NIMHANS)  Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periyasamy","family":"Govindaraj","sequence":"additional","affiliation":[{"name":"Neuromuscular laboratory, Department of Neuropathology National Institute of Mental Health and Neurosciences (NIMHANS)  Bengaluru Karnataka 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