Novel compound heterozygous DOCK6 variants expand the mutational spectrum in prenatal diagnosis of Adams-Oliver syndrome 2.

IF 2.1 4区医学 Q3 GENETICS & HEREDITY

BMC Medical Genomics Pub Date : 2025-06-06 DOI:10.1186/s12920-025-02157-w

Xue Zhong, Xuan Zheng, Yinglei Xv, Kangxi Cai, Qianqian Wang, Shiguo Liu

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引用次数: 0

Abstract

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.

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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。

背景：亚当斯-奥利弗综合征（Adams-Oliver syndrome， AOS）是一种罕见的发育障碍，DOCK6基因是已鉴定的AOS基因。本报告强调了AOS-2的产前诊断超声检查和基因检测。方法：对双侧脑室肿大、室旁钙化和室间隔缺损的生长受限胎儿进行三全外显子组测序（trio-WES）。通过迷你基因分析和蛋白质结构建模对剪接改变变体进行功能验证。结果：Trio-WES显示复合杂合DOCK6变异体：父移码(c.3190_3191del；p. Leu1064Valfs60)和母体剪接位点变异（c.3241-1G >t）。Minigene实验表明，c.3241-1G > T导致内含子26保留（486 bp），引入一个过早终止密码子（p. Val1081Glufs37）。结构建模证实了两个截断蛋白中关键DHR2结构域的缺失。结论：本研究扩大了DOCK6的突变谱，强调了将产前影像学与功能基因组学相结合对AOS2早期诊断的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Medical Genomics 医学-遗传学

CiteScore

3.90

自引率

0.00%

发文量

243

审稿时长

3.5 months

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.