Zhong Xue, Zheng Xuan, Xv Yinglei, Cai Kangxi, Wang Qianqian, Liu Shiguo
Medical Genetic Department, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, China.
BMC Med Genomics. 2025 Jun 6;18(1):104. doi: 10.1186/s12920-025-02157-w.
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.
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.
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.
This study expands the mutational spectrum of DOCK6 and underscores the importance of combining prenatal imaging with functional genomics for early diagnosis of AOS2.
亚当斯 - 奥利弗综合征（AOS）是一种罕见的发育障碍，DOCK6基因是已确定的AOS相关基因。本报告重点介绍了通过超声检查和基因检测对AOS - 2进行产前诊断的情况。
对一名生长受限、伴有双侧脑室扩大、室周钙化和室间隔缺损的胎儿进行了三联全外显子组测序（trio - WES）。通过小基因检测和蛋白质结构建模对剪接改变变异体进行功能验证。
三联全外显子组测序揭示了DOCK6基因的复合杂合变异：父系移码变异（c.3190_3191del；p.Leu1064Valfs60）和母系剪接位点变异（c.3241 - 1G>T）。小基因检测表明，c.3241 - 1G>T导致内含子26保留（486 bp），引入了一个提前终止密码子（p.Val1081Glufs37）。结构建模证实了两种截短蛋白中关键的DHR2结构域缺失。
本研究扩展了DOCK6基因的突变谱，并强调了将产前影像学与功能基因组学相结合对早期诊断AOS2的重要性。
