{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T04:34:51Z","timestamp":1768192491000,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,7,7]],"date-time":"2014-07-07T00:00:00Z","timestamp":1404691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008578","name":"Georgia Regents University","doi-asserted-by":"crossref","award":["20050-04330000-11600-64010-STARTUP00097"],"award-info":[{"award-number":["20050-04330000-11600-64010-STARTUP00097"]}],"id":[{"id":"10.13039\/100008578","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>Coffin\u2013Lowry syndrome (CLS) is a rare X\u2010linked dominant disorder characterized by intellectual disability, craniofacial abnormalities, short stature, tapering fingers, hypotonia, and skeletal malformations. CLS is caused by mutations in the Ribosomal Protein S6 Kinase, 90\u2009kDa, Polypeptide 3 (<jats:italic>RPS6KA3<\/jats:italic>) gene located at Xp22.12, which encodes Ribosomal S6 Kinase 2 (RSK2). Here we analyzed <jats:italic>RPS6KA3<\/jats:italic> in three unrelated CLS patients including one from the historical Coffin\u2013Lowry syndrome family and found two novel mutations. To date, over 140 mutations in <jats:italic>RPS6KA3<\/jats:italic> have been reported. However, the etiology of the very first familial case, which was described in 1971 by Lowry with detailed phenotype and coined the term CLS, has remained unknown. More than 40 years after the report, we succeeded in identifying deposited fibroblast cells from one patient of this historic family and found a novel heterozygous 216\u2009bp in\u2010frame deletion, encompassing exons 15 and 16 of <jats:italic>RPS6KA3<\/jats:italic>. Drop episodes in CLS patients were reported to be associated with truncating mutations deleting the C\u2010terminal kinase domain (KD), and only one missense mutation and one single basepair duplication involving the C\u2010terminal KD of RSK2 in the patients with drop episode have been reported thus far. Here we report the first in\u2010frame deletion in C\u2010terminal KD of <jats:italic>RPS6KA3<\/jats:italic> in a CLS patient with drop episodes. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36488","type":"journal-article","created":{"date-parts":[[2014,7,7]],"date-time":"2014-07-07T20:11:33Z","timestamp":1404763893000},"page":"2172-2179","source":"Crossref","is-referenced-by-count":17,"title":["The historical Coffin\u2013Lowry syndrome family revisited: Identification of two novel mutations of <i>RPS6KA3<\/i> in three male patients"],"prefix":"10.1002","volume":"164","author":[{"given":"Hiromi Koso","family":"Nishimoto","sequence":"first","affiliation":[{"name":"Section of Reproductive Endocrinology, Infertility &amp; Genetics, Department of Obstetrics and Gynecology Institute of Molecular Medicine and Genetics Medical College of Georgia, Georgia Regents University Augusta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyungsoo","family":"Ha","sequence":"additional","affiliation":[{"name":"Section of Reproductive Endocrinology, Infertility &amp; Genetics, Department of Obstetrics and Gynecology Institute of Molecular Medicine and Genetics Medical College of Georgia, Georgia Regents University Augusta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie R.","family":"Jones","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood South Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alka","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood South Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun\u2010Min","family":"Cho","sequence":"additional","affiliation":[{"name":"Section of Reproductive Endocrinology, Infertility &amp; Genetics, Department of Obstetrics and Gynecology Institute of Molecular Medicine and Genetics Medical College of Georgia, Georgia Regents University Augusta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence C.","family":"Layman","sequence":"additional","affiliation":[{"name":"Section of Reproductive Endocrinology, Infertility &amp; Genetics, Department of Obstetrics and Gynecology Institute of Molecular Medicine and Genetics Medical College of Georgia, Georgia Regents University Augusta Georgia"},{"name":"Neuroscience Program Medical College of Georgia, Georgia Regents University Augusta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyung\u2010Goo","family":"Kim","sequence":"additional","affiliation":[{"name":"Section of Reproductive Endocrinology, Infertility &amp; Genetics, Department of Obstetrics and Gynecology Institute of Molecular Medicine and Genetics Medical College of Georgia, Georgia Regents University Augusta Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,7,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2509"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3935"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202663200"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200102)17:2<103::AID-HUMU2>3.0.CO;2-N"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00660.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(99)00061-1"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.10.705"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10574"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/302153"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2010.07.006"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1971.02100170078009"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.11.890"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.05.016"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2004.02.015"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-007-0424-1"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.189"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-006-9116-1"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36299"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110289"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07423.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/384567a0"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00344-7"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1086\/340607"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710676105"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210368200"}],"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.36488","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36488","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T14:46:09Z","timestamp":1700664369000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,7]]},"references-count":25,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1002\/ajmg.a.36488"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36488","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,7]]}}}