{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:48:42Z","timestamp":1785473322078,"version":"3.56.0"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Defects in <jats:italic>RARS2<\/jats:italic> cause cerebellopontine hypoplasia type 6 (pontocerebellar hypoplasia type 6, PCH6, OMIM: #611523), a rare autosomal recessive inherited mitochondrial disease. Here, we report two male patients and their respective family histories.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe the clinical presentation and magnetic resonance imaging (MRI) findings of these patients. Whole\u2010exome sequencing was used to identify the genetic mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One patient showed hypoglycemia, high lactic acid levels (fluctuating from 6.7 to 14.1\u2009mmol\/L), and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and pons. The other patient presented with early infantile developmental and epileptic encephalopathies (EIDEEs) with an initial developmental delay followed by infantile epileptic spasm syndrome (IESS) at 5\u2009months old, with no imaging changes. Whole\u2010exome sequencing identified compound heterozygous <jats:italic>RARS2<\/jats:italic> variants c.25A&gt;G (p.I9V) with c.1261C&gt;T (p.Q421*) and c.1A&gt;G (p.M1V) with c.122A&gt;G (p.D41G) in these two patients. Of these loci, c.1261C&gt;T and c.122A&gt;G have not been previously reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our findings have expanded the <jats:italic>RARS2<\/jats:italic> gene variant spectrum and present EIDEEs and IESS as phenotypes which deepened the association between PCH6 and <jats:italic>RARS2.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Defects in RARS2 cause cerebellopontine hypoplasia type 6, a rare autosomal recessive inherited mitochondrial disease. Two patients with RARS2 variants were reported in this article. One patient showed hypoglycemia, high lactic acid levels, and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and Page 3 of 21 Epilepsia OpenFor Review Only pons. The other patient presented with an initial developmental delay followed by refractory epilepsy at 5 months old, with no imaging changes. Our findings deepened the association between PCH6 and RARS2.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12862","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T20:12:00Z","timestamp":1701115920000},"page":"250-257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical and genetic analysis of infants with pontocerebellar hypoplasia type 6 caused by <scp><i>RARS2<\/i><\/scp> variations"],"prefix":"10.1002","volume":"9","author":[{"given":"Shichao","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Third Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofei","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Third Affiliated Hospital of Zhengzhou University  Zhengzhou 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