Department of Pediatrics, Division of Neurology at the University of Alabama at Birmingham and Children's of Alabama, Birmingham, Alabama, USA.
Department of Pediatrics, Division of Pediatric Hematology and Oncology at the University of Alabama at Birmingham and Children's of Alabama, Birmingham, Alabama, USA.
Hum Mutat. 2022 Sep;43(9):1149-1161. doi: 10.1002/humu.24398. Epub 2022 May 20.
The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues. Recent advances in whole-genome sequencing of patients with undiagnosed genetic disorders have identified several rare pathogenic variants in DOCK genes. We conducted a systematic review and performed a patient database and literature search of reported DOCK pathogenic variants that have been identified in association with clinical pathologies such as global developmental delay, immune cell dysfunction, muscle hypotonia, and muscle ataxia among other categories. We then categorized these pathogenic DOCK variants and their associated clinical phenotypes under several unique categories: developmental, cardiovascular, metabolic, cognitive, or neuromuscular. Our systematic review of DOCK variants aims to identify and analyze potential DOCK-regulated networks associated with neuromuscular diseases and other disease pathologies, which may identify novel therapeutic strategies and targets. This systematic analysis and categorization of human-associated pathologies with DOCK pathogenic variants is the first report to the best of our knowledge for a unique class in this understudied gene family that has important implications in furthering personalized genomic medicine, clinical diagnoses, and improve targeted therapeutic outcomes across many clinical pathologies.
细胞分裂（DOCK）家族的基因（DOCK1-11）是多种细胞类型和组织中细胞迁移、生长和融合的重要介质。对未确诊遗传疾病患者的全基因组测序的最新进展已经确定了 DOCK 基因中的几个罕见的致病性变体。我们进行了系统评价，并对报道的与临床病理学相关的 DOCK 致病性变体进行了患者数据库和文献搜索，这些变体与包括全球发育迟缓、免疫细胞功能障碍、肌肉张力减退和肌肉共济失调等在内的其他类别有关。然后，我们将这些致病性 DOCK 变体及其相关的临床表型归类为几个独特的类别：发育、心血管、代谢、认知或神经肌肉。我们对 DOCK 变体的系统评价旨在识别和分析与神经肌肉疾病和其他疾病病理学相关的潜在 DOCK 调节网络，这可能确定新的治疗策略和靶点。这种对与 DOCK 致病性变体相关的人类相关疾病的系统分析和分类是我们所知的该研究不足的基因家族中的一个独特类别中的首次报告，对进一步推进个性化基因组医学、临床诊断以及改善许多临床病理学中的靶向治疗结果具有重要意义。
