{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:24:35Z","timestamp":1785183875026,"version":"3.55.0"},"reference-count":21,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Syndromol"],"published-print":{"date-parts":[[2022]]},"abstract":"Pontocerebellar hypoplasia (PCH) is a heterogeneous neurodevelopmental disorder that is characterized by decreased brainstem and cerebellum volume. Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease associated with autosomal recessive inheritance that results from mutations in the <i>RARS2<\/i> gene. In this case report, we describe a new clinical presentation with a novel <i>RARS2<\/i> pathogenic variant. We report here on 2 siblings who presented with neonatal lactic acidosis, microcephaly, growth retardation, persistent seizures, and cholestasis with a previously undefined <i>RARS2<\/i> pathogenic variant. In our literature review, we evaluated the clinical features and pathogenic variants of 34 patients reported in 16 publications since the initial identification of <i>RARS2<\/i> pathogenic variants in PCH6 in 2007. Both siblings were detected with c.1564G&#x3e;A (p.Val522Ile), a novel homozygous pathogenic variant of the <i>RARS2<\/i> gene. Imaging revealed advanced cerebral atrophy and cerebellar hypoplasia, while the basal ganglia and pons were preserved. At follow-up, the elevations in liver function test results and cholestasis had regressed while the LDH and GGT elevations persisted. Both siblings showed microcephaly on follow-up and started to suffer seizures. Severe developmental delay and nutritional problems were observed, and both died in infancy. <i>RARS2<\/i> pathogenic variant is a mitochondrial disease that causes severe mental, motor, and developmental retardation, as well as short life expectancy. Our patients are the first cases with liver involvement in PCH6 and a novel homozygous <i>RARS2<\/i> pathogenic variant to be reported in the literature. This additional phenotype can be considered as making a valid contribution to the literature. <\/jats:p>","DOI":"10.1159\/000519604","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T22:00:56Z","timestamp":1643752856000},"page":"226-234","source":"Crossref","is-referenced-by-count":4,"title":["A Patient with a Novel <b><i>RARS2<\/i><\/b> Variant Exhibiting Liver Involvement as a New Clinical Feature and Review of the Literature"],"prefix":"10.1159","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1001-7255","authenticated-orcid":false,"given":"Selin","family":"Sevin\u00e7","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131","family":"\u0130nci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih S.","family":"Ezg\u00fc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma T.","family":"Emino\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,2,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-016-9827-9"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9487-9"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200001)15:1%3c7::AID-HUMU4%3e3.0.CO;2-N"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1086\/521227"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2013_230"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9413-6"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000123"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2013-304308"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000209"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.31"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0525-9"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12108"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2019.103766"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13358"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2016.02.012"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33531"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2016_584"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.123"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.5491"}],"container-title":["Molecular Syndromology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/519604","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/519604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:26:56Z","timestamp":1745422016000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000519604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,5,2]]},"published-print":{"date-parts":[[2022,4,26]]}},"URL":"https:\/\/doi.org\/10.1159\/000519604","archive":["Portico"],"relation":{},"ISSN":["1661-8769","1661-8777"],"issn-type":[{"value":"1661-8769","type":"print"},{"value":"1661-8777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}