{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:30:07Z","timestamp":1770838207986,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Meckel\u2010Gruber syndrome (MKS, OMIM 24,900), also known as Meckel syndrome, is a rare and severe autosomal recessive disorder. The syndrome is typically characterized by a triad of occipital encephalocele, bilateral renal cystic dysplasia, and postaxial polydactyly. MKS shows significant clinical heterogeneity, which poses challenges for accurate prenatal diagnosis. Prenatal ultrasound is an important tool for detecting potential cases, but the complexity of MKS often requires additional advanced techniques such as prenatal whole\u2010exome sequencing (WES) to provide more accurate molecular genetic evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we used whole\u2010exome sequencing (WES) to analyze the genetic causes of suspected MKS in a Chinese fetus. Sanger sequencing was used to confirm the origin of the variants. The classification of variants was carried out in accordance with the guidelines of the American College of Medical Genetics and Genomics\/Association for Molecular Pathology (ACMG\/AMP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A 26\u2010year\u2010old pregnant woman was referred to our antenatal centre for genetic diagnosis at 13\u2009+\u20095\u2009weeks of gestation due to fetal occipital encephalocele and renal cysts detected by ultrasound. Two novel heterozygous variants, c.1047delA (p.Val351fs*1) and c.1336C&gt;T (p.Arg446*), were identified in\n                      <jats:italic>TCTN2<\/jats:italic>\n                      . Sanger sequencing revealed that the c.1047delA (p.Val351fs*1) variant was inherited from the mother and the c.1336C&gt;T (p.Arg446*) variant was inherited from the father. According to the ACMG\/AMP guidelines, these two variants were evaluated as pathogenic.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study further expands the genetic mutation spectrum of\n                      <jats:italic>TCTN2<\/jats:italic>\n                      and is conducive to further clarifying the relationship between the genotype and phenotype of MKS8. Severe variants in the\n                      <jats:italic>TCTN2<\/jats:italic>\n                      gene appear to be more likely to lead to MKS8. Clinically, the triad is an important basis for the diagnosis of MKS8, while other variable phenotypes of MKS8 can provide additional information for prenatal diagnosis. The combination of prenatal ultrasound and WES can provide a more comprehensive and accurate diagnosis of MKS8, which will greatly aid support for early intervention and treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70160","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T13:59:50Z","timestamp":1764424790000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Compound Heterozygous Variants in the\n                    <scp>\n                      <i>TCTN2<\/i>\n                    <\/scp>\n                    Gene Causing Meckel\u2013Gruber Syndrome 8 in a Non\u2010Consanguineous Chinese Family"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1849-0100","authenticated-orcid":false,"given":"Qi","family":"Yang","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Birth Defects Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis Center Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2175-2289","authenticated-orcid":false,"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Birth Defects Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-7701","authenticated-orcid":false,"given":"Sheng","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Birth Defects Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xunzhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Birth Defects Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Birth Defects Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Birth Defects Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3423-2845","authenticated-orcid":false,"given":"Qinle","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Birth Defects Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingsi","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Department of Genetic and Metabolic Central Laboratory Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Birth Defects Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"},{"name":"Guangxi Clinical Research Center for Pediatric Diseases Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region  Nanning China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68558"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102015\u2010103469"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102015\u2010103087"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028175"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2021.101035"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2410"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.06.003"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010023\u201001669\u20107"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.891"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.377"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2017.00244"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010023\u201001143\u20103"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.160"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001559\u20105"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010012\u20100951\u20102"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021108843"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002416"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62119"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2023.100866"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3233\/TRD\u2010190041"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.73"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211\u20105463.12651"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201911062"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.04.019"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110811"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14177"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21507"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010016\u20101099\u20105"},{"issue":"4","key":"e_1_2_12_31_1","first-page":"415","article-title":"Progress on Hedgehog Signaling Transduction","volume":"66","author":"Tang Y.","year":"2014","journal-title":"Sheng Li Xue Bao"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2017.08.003"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2018.04.051"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005627"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010020\u20100804\u20100"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70160","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70160","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70160","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:56:38Z","timestamp":1770836198000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,29]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/mgg3.70160"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70160","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,29]]},"assertion":[{"value":"2024-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70160"}}