{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:55:54Z","timestamp":1790420154245,"version":"4.1.0"},"reference-count":6,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T00:00:00Z","timestamp":1597104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU 1240\/10\u20101"],"award-info":[{"award-number":["KU 1240\/10\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01DQ17003"],"award-info":[{"award-number":["01DQ17003"]}],"id":[{"id":"10.13039\/501100002347","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":[[2020,11]]},"abstract":"Abstract<\/jats:title>Roberts syndrome (also known as Roberts\u2010SC phocomelia syndrome) is an autosomal recessive developmental disorder, characterized by pre\u2010 and postnatal growth retardation, limb malformations including bilateral symmetric tetraphocomelia or mesomelia, and craniofacial dysmorphism. Biallelic loss\u2010of\u2010function variants in ESCO2<\/jats:italic>, which codes for establishment of sister chromatid cohesion N\u2010acetyltransferase 2, cause Roberts syndrome. Phenotypic spectrum among patients is broad, challenging clinical diagnosis in mildly affected individuals. Here we report a 3\u2010year\u2010old boy with a mild phenotype of Roberts syndrome with bilateral elbow contractures, humeroradial synostosis, mild lower limb disparity, and facial dysmorphism. Trio whole\u2010exome sequencing identified the novel biallelic splice variant c.1673+1G>A in ESCO2<\/jats:italic> in the patient. Aberrant ESCO2<\/jats:italic> pre\u2010mRNA splicing, reduced relative ESCO2<\/jats:italic> mRNA amount, and characteristic cytogenetic defects, such as premature centromere separation, heterochromatin repulsion, and chromosome breaks, in patient cells strongly supported pathogenicity of the ESCO2<\/jats:italic> variant affecting one of the highly conserved guanine\u2010thymine dinucleotide of the donor splice site. Our case highlights the difficulty in establishing a clinical diagnosis in individuals with minor clinical features of Roberts syndrome and normal intellectual and social development. However, next\u2010generation sequencing tools allow for molecular diagnosis in cases presenting with mild developmental defects.<\/jats:p>","DOI":"10.1002\/ajmg.a.61826","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T06:02:07Z","timestamp":1597212127000},"page":"2793-2796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2<\/i>"],"prefix":"10.1002","volume":"182","author":[{"given":"Pauline E.","family":"Schneeberger","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-7031","authenticated-orcid":false,"given":"Shalini S.","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-8963","authenticated-orcid":false,"given":"Kerstin","family":"Kutsche","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-8239","authenticated-orcid":false,"given":"Katta M.","family":"Girisha","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33261"},{"key":"e_1_2_8_3_1","volume-title":"GeneReviews","author":"Gordillo M.","year":"1993"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/498695"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.12.013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.068395"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1548"}],"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.61826","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61826","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.61826","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61826","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T05:56:53Z","timestamp":1693720613000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,11]]},"references-count":6,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/ajmg.a.61826"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61826","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,11]]},"assertion":[{"value":"2020-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}