{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:59:35Z","timestamp":1790215175875,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060388"],"award-info":[{"award-number":["82060388"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101796"],"award-info":[{"award-number":["82101796"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201884"],"award-info":[{"award-number":["82201884"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004001","name":"Guizhou Science and Technology Department","doi-asserted-by":"publisher","award":["QKHJC[2020]1Y424"],"award-info":[{"award-number":["QKHJC[2020]1Y424"]}],"id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Acid ceramidase (ACDase) deficiency is an ultrarare autosomal recessive lysosomal disorder caused by pathogenic N\u2010acylsphingosine amidohydrolase (<jats:italic>ASAH1<\/jats:italic>) variants. It presents with either Farber disease (FD) or spinal muscular atrophy with progressive myoclonic epilepsy (SMA\u2010PME).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The study aims to identify a novel splice site variant in a hydrops fetus that causes <jats:italic>ASAH1<\/jats:italic>\u2010related disorder, aid genetic counseling, and accurate prenatal diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a case of hydrops fetalis with a novel homozygous mutation in <jats:italic>ASAH1<\/jats:italic> inherited from non\u2010consanguineous parents. We performed copy number variation sequencing (CNV\u2010Seq) and whole exome sequencing (WES) on the fetus and family, respectively. Minigene splicing analyses were conducted to confirm the pathogenic variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WES data revealed a splice site variant of the <jats:italic>ASAH1<\/jats:italic> (c.458\u20102A&gt;T), which was predicted to affect RNA splicing. Minigene splicing analyses found that the c.458\u20102A&gt;T variant abolished the canonical splicing of intron 6, thereby activating two cryptic splicing products (c.456_458ins56bp and c.458_503del).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, we identified a novel splice site variant in the mutational spectrum of <jats:italic>ASAH1<\/jats:italic> and its aberrant effect on splicing. These findings highlight the importance of ultrasonic manifestation and family history of fetal hydrops during <jats:italic>ASAH1<\/jats:italic>\u2010related disorders and could also aid genetic counseling and accurate prenatal diagnosis. To the best of our knowledge, this is the shortest\u2010lived account of <jats:italic>ASAH1<\/jats:italic>\u2010related disorders in utero with severe hydrops fetalis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2317","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T13:14:04Z","timestamp":1699967644000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional analysis of a novel splice site variant in the <scp>ASAH1<\/scp> gene"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5676-9052","authenticated-orcid":false,"given":"Shujuan","family":"Yan","sequence":"first","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Fu","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-5065","authenticated-orcid":false,"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibin","family":"Huang","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Wang","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-136X","authenticated-orcid":false,"given":"Can","family":"Liao","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201202301"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.04.019"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61752"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12316"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39659"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204841"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4586"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1546-0096-5-15"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7016com"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-145508"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24056"},{"issue":"4","key":"e_1_2_12_13_1","first-page":"499","article-title":"A lipid metabolic disorder: Disseminated lipogranulomatosis; 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