{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:12:13Z","timestamp":1791663133611,"version":"4.3.4"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974240 81970829 82171711"],"award-info":[{"award-number":["81974240 81970829 82171711"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019081","name":"Science and Technology Program of Hunan Province","doi-asserted-by":"publisher","award":["2019SK1010 2019SK1014"],"award-info":[{"award-number":["2019SK1010 2019SK1014"]}],"id":[{"id":"10.13039\/501100019081","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>Seckel syndrome (SCKL) is a rare autosomal recessive inherited disorder, which is mainly characterized by intrauterine and postnatal growth restrictions, microcephaly, intellectual disability, and a typical \u201cbird-head\u201d facial appearance. Here, we aimed to identify the genetic etiology of a family with suspected SCKL.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>This study enrolled a Chinese family suspected of SCKL with their detailed family history and clinical data. We performed karyotype analysis, copy number variation sequencing (CNV-seq), and trio whole-exome sequencing (WES) to explore the genetic etiology in the proband. Furthermore, the quantitative real-time polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) were conducted to confirm the pathogenicity of novel variants.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>The karyotype analysis and CNV-seq were normal in the proband. Two novel variants in<jats:italic>CEP152<\/jats:italic>, c.1060C&amp;gt;T (p.Arg354*) and c.1414-14A&amp;gt;G, were identified in the proband through trio-WES. The qPCR results showed that the total<jats:italic>CEP152<\/jats:italic>mRNA expression levels were significantly reduced in c.1060C&amp;gt;T (p.Arg354*) and c.1414-14A&amp;gt;G compared with healthy control individuals. Moreover, aberrant skipping of exon 12 due to the non-canonical splice-site variant was revealed by RT-PCR and Sanger sequencing.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold>Our findings expanded pathogenic variant spectra in SCKL and offered new insights into the pathogenicity of a non-classical splice-site variant in<jats:italic>CEP152<\/jats:italic>, which provided additional information for helping the family improve pregnancy plans in the future.<\/jats:p>","DOI":"10.3389\/fgene.2022.1052915","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T07:35:37Z","timestamp":1672817737000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Two novel variants in CEP152 caused Seckel syndrome 5 in a Chinese family"],"prefix":"10.3389","volume":"13","author":[{"given":"Li","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1002\/humu.23626","article-title":"Recommendations for interpreting the loss of function pvs1 acmg\/amp variant criterion","volume":"39","author":"Abou Tayoun","year":"2018","journal-title":"Hum. 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