{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T01:44:45Z","timestamp":1772502285592,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T00:00:00Z","timestamp":1684022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biallelic variants in <jats:italic>CHST3<\/jats:italic> gene result in congenital dislocation of large joints, club feet, short stature, rhizomelia, kypho\u2010scoliosis, platyspondyly, epiphyseal dysplasia, flared metaphysis, in addition to minor cardiac lesions and hearing loss. Herein, we describe 14 new patients from 11 unrelated Egyptian families with <jats:italic>CHST3<\/jats:italic>\u2010related skeletal dysplasia. All patients had spondyloepiphyseal changes that were progressive with age in addition to bifid distal ends of humeri which can be considered a diagnostic key in patients with <jats:italic>CHST3<\/jats:italic> variants. They also shared peculiar facies with broad forehead, broad nasal tip, long philtrum and short neck. Rare unusual associated findings included microdontia, teeth spacing, delayed eruption, prominent angulation of the lumbar\u2010sacral junction and atrial septal defect. Mutational analysis revealed 10 different homozygous <jats:italic>CHST3<\/jats:italic> (NM_004273.5) variants including 7 missense, two frameshift and one nonsense variant. Of them, the c.384_391dup (p.Pro131Argfs*88) was recurrent in two families. Eight of these variants were not described before. Our study presents the largest series of patients with <jats:italic>CHST3<\/jats:italic>\u2010related skeletal dysplasia from the same ethnic group. Furthermore, it reinforces that lethal cardiac involvement is a critical clinical finding of the disorder. Therefore, we believe that our study expands the phenotypic and mutational spectrum, and also highlights the importance of performing echocardiography in patients harboring <jats:italic>CHST3<\/jats:italic> variants.<\/jats:p>","DOI":"10.1002\/ajmg.a.63246","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T06:09:29Z","timestamp":1684130969000},"page":"2100-2112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp><i>CHST3<\/i><\/scp>\u2010related skeletal dysplasia in 14 patients: Identification of 8 novel variants and further expansion of the phenotypic spectrum"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2313-7387","authenticated-orcid":false,"given":"Ghada A.","family":"Otaify","sequence":"first","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-6619","authenticated-orcid":false,"given":"Rasha M.","family":"Elhossini","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherif F.","family":"Abdel\u2010Ghafar","sequence":"additional","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8028-8566","authenticated-orcid":false,"given":"Inas M.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Orodental Genetics Department, Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghada M. H.","family":"Abdel\u2010Salam","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona S.","family":"Aglan","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-0147","authenticated-orcid":false,"given":"Mohamed S.","family":"Abdel\u2010Hamid","sequence":"additional","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000295"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20440"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01202412-199701000-00003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.05.006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijri.IJRI_367_16"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-022-05719-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1974.02110220105015"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30179"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61366"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.800"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20606"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12885"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000021"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37996"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400334101"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01167.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33641"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32482"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12694"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.21037\/aoj.2017.01.02"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63246","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T12:23:45Z","timestamp":1692793425000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,14]]},"references-count":20,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/ajmg.a.63246"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63246","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,14]]},"assertion":[{"value":"2022-12-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}