{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:45:29Z","timestamp":1780109129052,"version":"3.54.0"},"reference-count":21,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:00:00Z","timestamp":1641340800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>POLG pathogenic variants are the commonest single-gene cause of inherited mitochondrial disease. However, the data on clinicogenetic associations in POLG-related disorders are sparse. This study maps the clinicogenetic spectrum of POLG-related disorders in the pediatric population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Individuals were recruited across 6 centers in India. Children diagnosed between January 2015 and August 2020 with pathogenic or likely pathogenic POLG variants and age of onset &lt;15 years were eligible. Phenotypically, patients were categorized into Alpers-Huttenlocher syndrome; myocerebrohepatopathy syndrome; myoclonic epilepsy, myopathy, and sensory ataxia; ataxia-neuropathy spectrum; Leigh disease; and autosomal dominant \/ recessive progressive external ophthalmoplegia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 3729 genetic reports and 4256 hospital records were screened. Twenty-two patients with pathogenic variants were included. Phenotypically, patients were classifiable into Alpers-Huttenlocher syndrome (8\/22; 36.4%), progressive external ophthalmoplegia (8\/22; 36.4%), Leigh disease (2\/22; 9.1%), ataxia-neuropathy spectrum (2\/22; 9.1%), and unclassified (2\/22; 9.1%). The prominent clinical manifestations included developmental delay (n\u2009=\u200914; 63.7%), neuroregression (n\u2009=\u200914; 63.7%), encephalopathy (n\u2009=\u200911; 50%), epilepsy (n\u2009=\u200911; 50%), ophthalmoplegia (n\u2009=\u20098; 36.4%), and liver dysfunction (n\u2009=\u20098; 36.4%). Forty-four pathogenic variants were identified at 13 loci, and these were clustered at exonuclease (18\/44; 40.9%), linker (13\/44; 29.5%), polymerase (10\/44; 22.7%), and N-terminal domains (3\/44; 6.8%). Genotype-phenotype analysis suggested that serious outcomes including neuroregression (odds ratio [OR] 11, 95% CI 2.5, 41), epilepsy (OR 9, 95% CI 2.4, 39), encephalopathy (OR 5.7, 95% CI 1.4, 19), and hepatic dysfunction (OR 4.6, 95% CI 21.3, 15) were associated with at least 1 variant involving linker or polymerase domain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We describe the clinical subgroups and their associations with different POLG domains. These can aid in the development of follow-up and management strategies of presymptomatic individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/08830738211067065","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T14:23:37Z","timestamp":1641392617000},"page":"246-255","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical and molecular spectrum associated with Polymerase-\u03b3 related disorders"],"prefix":"10.1177","volume":"37","author":[{"given":"Ruchika","family":"Jha","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Armed Forces Medical College, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshkumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Zydus Hospital, Ahmedabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachana","family":"Dubey","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Medanta Hospital, Indore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8537-7338","authenticated-orcid":false,"given":"Jyotindra N.","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Army Hospital (Research & Referral), New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandana","family":"Bhagwat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Neurology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-0736","authenticated-orcid":false,"given":"Lokesh","family":"Saini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Neurology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjith","family":"K. Manokaran","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Neurology, Sri Ramachandra Institute of Higher Education, Chennai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biju M.","family":"John","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Armed Forces Medical College, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uday B.","family":"Kovilapu","sequence":"additional","affiliation":[{"name":"Department of Radiodiagnosis, Armed Forces Medical College, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneesh","family":"Mohimen","sequence":"additional","affiliation":[{"name":"Department of Radiodiagnosis, Command Hospital (Central Command), Lucknow, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apoorv","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Armed Forces Medical College, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2367-6591","authenticated-orcid":false,"given":"Vishal","family":"Sondhi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Armed Forces Medical College, Pune, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,1,5]]},"reference":[{"key":"bibr1-08830738211067065","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2003.09"},{"key":"bibr2-08830738211067065","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl088"},{"key":"bibr3-08830738211067065","doi-asserted-by":"publisher","DOI":"10.1097\/NRL.0b013e3181c78a89"},{"key":"bibr4-08830738211067065","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2008.02059.x"},{"key":"bibr5-08830738211067065","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.35"},{"key":"bibr6-08830738211067065","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011395"},{"key":"bibr7-08830738211067065","doi-asserted-by":"publisher","DOI":"10.1038\/90034"},{"key":"bibr8-08830738211067065","volume-title":"GeneReviews(R). 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