{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T09:48:06Z","timestamp":1782726486116,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005358","name":"ACMG Foundation for Genetic and Genomic Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005358","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Biallelic pathogenic variants in\n                    <jats:italic>PNPT1<\/jats:italic>\n                    cause combined oxidative phosphorylation deficiency 13 (COXPD13) (MIM #614932), linking mitochondrial dysfunction to type I interferon (IFN) activation through cytosolic leakage of mitochondrial double\u2010stranded RNA (mt\u2010dsRNA). This mechanism connects mitochondrial disease to interferonopathies such as Aicardi\u2013Gouti\u00e8res syndrome (AGS). We describe a 7\u2010month\u2010old female infant with compound heterozygous\n                    <jats:italic>PNPT1<\/jats:italic>\n                    variants presenting with severe hypotonia, feeding difficulties necessitating gastrostomy, dystonia, and elevated serum lactate. Brain magnetic resonance imaging (MRI) demonstrated marked cerebellar, brainstem, and basal ganglia atrophy, with a lactate peak on MR spectroscopy (consistent with an inverted doublet). Serum immune profiling revealed a mild but elevated type I IFN signature. Given the mechanistic overlap with AGS, off\u2010label tofacitinib, a Janus kinase (JAK) inhibitor that blocks IFN\u2010driven JAK\/STAT signaling, was initiated following pediatric interferonopathy dosing protocols. Tofacitinib was associated with normalization of serum type I IFN biomarkers, reduction in lactate and transaminases, improvement in dystonic movements, ventilatory stability, and improved growth\/nutrition without treatment\u2010limiting adverse events. To our knowledge, this represents the first reported use of JAK inhibition in COXPD13. The observed clinical and biochemical stabilization supports defining COXPD13 as a \u201cmitochondrial interferonopathy\u201d and suggests that IFN\u2010signature screening may identify mitochondrial disease patients who could benefit from targeted immunomodulation.\n                  <\/jats:p>","DOI":"10.1002\/jmd2.70096","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T09:35:52Z","timestamp":1782725752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>JAK<\/scp>\n                    Inhibition in\n                    <scp>\n                      <i>PNPT1<\/i>\n                    <\/scp>\n                    \u2010Related Mitochondrial Interferonopathy: A Case Report and Review of Mitochondrial\u2013Immune Crosstalk"],"prefix":"10.1002","volume":"67","author":[{"given":"Dan Ross","family":"Brooks","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Yong","family":"Koh","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Division of Neurology Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0555-8783","authenticated-orcid":false,"given":"Taylor Martin","family":"Kerrins","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Bland","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Allergy &amp; Immunology, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Division of Allergy &amp; Immunology Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Kogan","family":"Nicholas","sequence":"additional","affiliation":[{"name":"Division of Allergy &amp; Immunology, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Division of Allergy &amp; Immunology Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Jean","family":"Sikkink","sequence":"additional","affiliation":[{"name":"Department of Pediatrics &amp; Internal Medicine Geisinger Medical Center  Danville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Kralik","sequence":"additional","affiliation":[{"name":"Department of Radiology Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Radiology Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Eng","sequence":"additional","affiliation":[{"name":"Baylor Genetics  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9781-3387","authenticated-orcid":false,"given":"Chaya Nautiyal","family":"Murali","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Lalani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar Lenglet","family":"Magoulas","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Emrick","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Division of Neurology Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen Sydney","family":"Fisher","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Division of Neurology Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3502-8460","authenticated-orcid":false,"given":"Fernando","family":"Scaglia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Baylor Genetics  Houston Texas USA"},{"name":"Joint BCM\u2013CUHK Center of Medical Genetics Prince of Wales Hospital  Hong Kong SAR 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2021 European Alliance of Associations for Rheumatology\/American College of Rheumatology Points to Consider for Diagnosis and Management of Autoinflammatory Type I Interferonopathies: CANDLE\/PRAAS, SAVI, and AGS","volume":"74","author":"Cetin Gedik K.","year":"2022","journal-title":"Arthritis and 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