{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:23:58Z","timestamp":1791195838364,"version":"4.1.0"},"reference-count":9,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T00:00:00Z","timestamp":1490140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["01GM1404"],"award-info":[{"award-number":["01GM1404"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Since the original description of the <jats:italic>IARS2<\/jats:italic>\u2010related cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, skeletal dysplasia syndrome (CAGSSS; OMIM 616007) in an extended consanguineous family of French\u2013Canadian descent, no further patients have been reported. <jats:italic>IARS2<\/jats:italic> (OMIM 612801) encodes the mitochondrial isoleucine\u2010tRNA synthetase which belongs to the class\u2010I aminoacyl\u2010tRNA synthetase family, and has been implicated in CAGSSS and a form of Leigh syndrome. Here, we report on a female Danish patient with a novel homozygous <jats:italic>IARS2<\/jats:italic> mutation, p.Gly874Arg, who presented at birth with bilateral hip dislocation and short stature. At 3 months, additional dysmorphic features were noted and at 18 months her radiographic skeletal abnormalities were suggestive of an underlying spondyloepimetaphyseal dysplasia (SEMD). Retrospective analysis of the neonatal radiographs confirmed that the skeletal changes were present at birth. It was only with time that several of the other manifestations of the CAGSSS emerged, namely, cataracts, peripheral neuropathy, and hearing loss. Growth hormone deficiency has not (yet) manifested. We present her clinical features and particularly highlight her skeletal findings, which confirm the presence of a primary SEMD skeletal dysplasia in a growing list of mitochondrial\u2010related disorders including CAGSSS, CODAS, EVEN\u2010PLUS, and X\u2010linked SEMD\u2010MR syndromes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38116","type":"journal-article","created":{"date-parts":[[2017,3,23]],"date-time":"2017-03-23T05:24:33Z","timestamp":1490246673000},"page":"1102-1108","source":"Crossref","is-referenced-by-count":25,"title":["Confirmation of CAGSSS syndrome as a distinct entity in a Danish patient with a novel homozygous mutation in <i>IARS2<\/i>"],"prefix":"10.1002","volume":"173","author":[{"given":"Shahida","family":"Moosa","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Haagerup","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Aarhus University Hospital Aarhus Denmark"},{"name":"Regional Hospital West Center for Research and Education Herning Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille Axel","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Aarhus University Hospital Aarhus Denmark"},{"name":"Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin Kastberg","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Radiology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Altm\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Cologne Cologne Germany"},{"name":"Cologne Center for Genomics (CCG) University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae\u2010Joon","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Pediatric Orthopaedics Seoul National University Children's Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ok\u2010Hwa","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiology Woorisoa Children's Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Pediatric Imaging Tokyo Metropolitan Children's Medical Center Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Wollnik","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37029"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000000847"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389300800312"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12792"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22753"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep17154"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22752"},{"key":"e_1_2_8_9_1","first-page":"1285","article-title":"Mutation in the nuclear\u2010encoded mitochondrial isoleucyl\u2010tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome","volume":"35","author":"Schwartzentruber J.","journal-title":"Human Mutation"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.12.003"}],"container-title":["American Journal of Medical Genetics Part 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