{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:41:23Z","timestamp":1790977283858,"version":"4.1.0"},"reference-count":7,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,7,15]],"date-time":"2010-07-15T00:00:00Z","timestamp":1279152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Six subtypes of autosomal recessive pontocerebellar hypoplasia (PCH) have been identified and the genetic basis of four of these (PCH1, PCH2, PCH4, and PCH6) is known. PCH6 is associated with cerebral atrophy and multiple but variable respiratory chain defects in muscle and has been reported in one consanguineous Sephardic Jewish family. It is caused by mutations in the <jats:italic>RARS2<\/jats:italic> gene which encodes mitochondrial arginine\u2010transfer RNA synthetase. Here we describe a female patient born to nonconsanguineous British parents. She presented in the neonatal period with increased respiratory rate, poor feeding and transiently elevated blood and CSF lactate levels. She went on to manifest profound developmental delay and severe microcephaly. Edema of the hands, feet, and face were suggestive of a PEHO\u2010like condition (<jats:italic>p<\/jats:italic>rogressive encephalopathy, <jats:italic>e<\/jats:italic>dema, <jats:italic>h<\/jats:italic>ypsarrhythmia and <jats:italic>o<\/jats:italic>ptic atrophy), although optic atrophy and hypsarrhythmia were absent. Cranial MRI at age 14 months showed generalized cerebral atrophy, thinning of the pons and gross atrophy and flattening of the cerebellar hemispheres. Muscle biopsies on two occasions were normal with normal respiratory chain studies. Despite the absence of respiratory chain defects, the phenotype was felt to be consistent with PCH6 and indeed two novel pathogenic <jats:italic>RARS2<\/jats:italic> mutations were identified. Ours is the second report of PCH6 due to <jats:italic>RARS2<\/jats:italic> mutations and demonstrates that respiratory chain abnormalities are not obligatory, whereas some features of PEHO might be present. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33531","type":"journal-article","created":{"date-parts":[[2010,7,15]],"date-time":"2010-07-15T16:26:43Z","timestamp":1279211203000},"page":"2079-2084","source":"Crossref","is-referenced-by-count":65,"title":["Pontocerebellar hypoplasia type 6: A British case with PEHO\u2010like features"],"prefix":"10.1002","volume":"152A","author":[{"given":"Julia","family":"Rankin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Dobyns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Harington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,7,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.204"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-973467"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/521227"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31095"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000068548.58498.41"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.07.006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.11.932"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.33531","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T20:08:53Z","timestamp":1696709333000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,20]]},"references-count":7,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["10.1002\/ajmg.a.33531"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33531","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,7,20]]}}}