{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:49:59Z","timestamp":1791413399910,"version":"4.3.3"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Silverman\u2013Handmaker type dyssegmental dysplasia (DDSH) is a rare and lethal skeletal dysplasia caused by biallelic null variations in the <jats:italic>HSPG2<\/jats:italic> gene, which encodes the extracellular matrix proteoglycan perlecan. Here, we report a prenatal case of DDSH identified at 18\u2009weeks of gestation, referred due to ultrasonographic findings of limb shortening, retrognathia, and irregularities in the lumbar vertebrae. Targeted skeletal dysplasia panel testing via next\u2010generation sequencing (NGS) revealed a novel homozygous splice site variant, c.1355\u2009+\u20091\u2009G&gt;T, located at the canonical donor site of intron 11 in <jats:italic>HSPG2<\/jats:italic>. The fetus died shortly after birth, consistent with the expected DDSH phenotype. Our case expands the mutational spectrum of <jats:italic>HSPG2\u2010<\/jats:italic>related skeletal dysplasias and underscores the diagnostic and prognostic challenges of novel splicing variants in prenatal genetic counseling. It also emphasizes the value of combining prenatal imaging with molecular diagnostics to improve diagnostic accuracy and support informed reproductive decision\u2010making.<\/jats:p>","DOI":"10.1002\/ajmg.a.64152","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T06:25:14Z","timestamp":1749709514000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prenatal Diagnosis of <scp>HSPG2<\/scp>\u2010Related Dyssegmental Dysplasia: The First Report From Turkey"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0160-0377","authenticated-orcid":false,"given":"Mehmet Berkay","family":"Akcan","sequence":"first","affiliation":[{"name":"Department of Medical Genetics \u0130zmir City Hospital  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raziye","family":"Torun","sequence":"additional","affiliation":[{"name":"Department of Perinatology Izmir City Hospital  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuba S\u00f6zen","family":"T\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics \u0130zmir City Hospital  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zg\u00fcr","family":"K\u0131rb\u0131y\u0131k","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics \u0130zmir City Hospital  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atalay","family":"Ekin","sequence":"additional","affiliation":[{"name":"Department of Perinatology Izmir City Hospital  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8366-6806","authenticated-orcid":false,"given":"Altu\u011f","family":"Ko\u00e7","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics \u0130zmir City Hospital  \u0130zmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320270208"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/340390"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/86941"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.379"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2024.101125"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010024\u201001229\u20106"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.09.003"},{"issue":"3","key":"e_1_2_9_9_1","first-page":"79","article-title":"Dyssegmental Dwarfism: A New Syndrome of Lethal Dwarfism","volume":"13","author":"Handmaker S. D.","year":"1977","journal-title":"Birth Defects Original Article Series"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4193"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes9110556"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/82638"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980113)75:2<164::AID-AJMG8>3.0.CO;2-T"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2010.06.005"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.6359"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20388"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63132"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.ceog4902037"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi8013938"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e3282f25136"}],"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.64152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:29:01Z","timestamp":1757500141000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.64152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/ajmg.a.64152"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.64152","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,12]]},"assertion":[{"value":"2025-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e64152"}}