Xue Zhong, Xuan Zheng, Yinglei Xv, Kangxi Cai, Qianqian Wang, Shiguo Liu
{"title":"新型复合杂合DOCK6变异扩大了亚当斯-奥利弗综合征产前诊断中的突变谱2。","authors":"Xue Zhong, Xuan Zheng, Yinglei Xv, Kangxi Cai, Qianqian Wang, Shiguo Liu","doi":"10.1186/s12920-025-02157-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Adams-Oliver syndrome (AOS) is a rare developmental disorder, and the DOCK6 gene is an identified AOS gene. This report highlights the prenatal diagnosis of AOS-2 by ultrasonography and genetic testing.</p><p><strong>Methods: </strong>A growth-restricted fetus with bilateral ventriculomegaly, paraventricular calcifications, and ventricular septal defect underwent trio-whole-exome sequencing (trio-WES). Functional validation of the splice-altering variant was performed via minigene assays and protein structural modeling.</p><p><strong>Results: </strong>Trio-WES revealed compound heterozygous DOCK6 variants: a paternal frameshift (c.3190_3191del; p. Leu1064Valfs60) and a maternal splice-site variant (c.3241-1G > T). Minigene assays demonstrated that c.3241-1G > T caused intron 26 retention (486 bp), introducing a premature termination codon (p. Val1081Glufs37). Structural modeling confirmed the loss of critical DHR2 domains in both truncated proteins.</p><p><strong>Conclusions: </strong>This study expands the mutational spectrum of DOCK6 and underscores the importance of combining prenatal imaging with functional genomics for early diagnosis of AOS2.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"104"},"PeriodicalIF":2.1000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144770/pdf/","citationCount":"0","resultStr":"{\"title\":\"Novel compound heterozygous DOCK6 variants expand the mutational spectrum in prenatal diagnosis of Adams-Oliver syndrome 2.\",\"authors\":\"Xue Zhong, Xuan Zheng, Yinglei Xv, Kangxi Cai, Qianqian Wang, Shiguo Liu\",\"doi\":\"10.1186/s12920-025-02157-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Adams-Oliver syndrome (AOS) is a rare developmental disorder, and the DOCK6 gene is an identified AOS gene. This report highlights the prenatal diagnosis of AOS-2 by ultrasonography and genetic testing.</p><p><strong>Methods: </strong>A growth-restricted fetus with bilateral ventriculomegaly, paraventricular calcifications, and ventricular septal defect underwent trio-whole-exome sequencing (trio-WES). Functional validation of the splice-altering variant was performed via minigene assays and protein structural modeling.</p><p><strong>Results: </strong>Trio-WES revealed compound heterozygous DOCK6 variants: a paternal frameshift (c.3190_3191del; p. Leu1064Valfs60) and a maternal splice-site variant (c.3241-1G > T). Minigene assays demonstrated that c.3241-1G > T caused intron 26 retention (486 bp), introducing a premature termination codon (p. Val1081Glufs37). Structural modeling confirmed the loss of critical DHR2 domains in both truncated proteins.</p><p><strong>Conclusions: </strong>This study expands the mutational spectrum of DOCK6 and underscores the importance of combining prenatal imaging with functional genomics for early diagnosis of AOS2.</p>\",\"PeriodicalId\":8915,\"journal\":{\"name\":\"BMC Medical Genomics\",\"volume\":\"18 1\",\"pages\":\"104\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144770/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Medical Genomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12920-025-02157-w\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medical Genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12920-025-02157-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Novel compound heterozygous DOCK6 variants expand the mutational spectrum in prenatal diagnosis of Adams-Oliver syndrome 2.
Background: Adams-Oliver syndrome (AOS) is a rare developmental disorder, and the DOCK6 gene is an identified AOS gene. This report highlights the prenatal diagnosis of AOS-2 by ultrasonography and genetic testing.
Methods: A growth-restricted fetus with bilateral ventriculomegaly, paraventricular calcifications, and ventricular septal defect underwent trio-whole-exome sequencing (trio-WES). Functional validation of the splice-altering variant was performed via minigene assays and protein structural modeling.
Results: Trio-WES revealed compound heterozygous DOCK6 variants: a paternal frameshift (c.3190_3191del; p. Leu1064Valfs60) and a maternal splice-site variant (c.3241-1G > T). Minigene assays demonstrated that c.3241-1G > T caused intron 26 retention (486 bp), introducing a premature termination codon (p. Val1081Glufs37). Structural modeling confirmed the loss of critical DHR2 domains in both truncated proteins.
Conclusions: This study expands the mutational spectrum of DOCK6 and underscores the importance of combining prenatal imaging with functional genomics for early diagnosis of AOS2.
期刊介绍：
BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
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