Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Division of Clinical Genetics, Children's Mercy Hospital, Kansas City, Missouri, USA.
Clin Genet. 2022 Feb;101(2):214-220. doi: 10.1111/cge.14085. Epub 2021 Nov 15.
Congenital heart defects (CHD) are the most commonly occurring birth defect and can occur in isolation or with additional clinical features comprising a genetic syndrome. Autosomal dominant variants in TAB2 are recognized by the American Heart Association as causing nonsyndromic CHD, however, emerging data point to additional, extra-cardiac features associated with TAB2 variants. We identified 15 newly reported individuals with pathogenic TAB2 variants and reviewed an additional 24 subjects with TAB2 variants in the literature. Analysis showed 64% (25/39) of individuals with disease resulting from TAB2 single nucleotide variants (SNV) had syndromic CHD or adult-onset cardiomyopathy with one or more extra-cardiac features. The most commonly co-occurring features with CHD or cardiomyopathy were facial dysmorphism, skeletal and connective tissue defects and most subjects with TAB2 variants present as a connective tissue disorder. Notably, 53% (8/15) of our cohort displayed developmental delay and we suspect this may be a previously unappreciated feature of TAB2 disease. We describe the largest cohort of subjects with TAB2 SNV and show that in addition to heart disease, features across multiple systems are present in most TAB2 cases. In light of our findings, we recommend that TAB2 be included on the list of genes that cause syndromic CHD, adult-onset cardiomyopathy, and connective tissue disorder.
先天性心脏病（CHD）是最常见的出生缺陷，可以单独发生，也可以伴有其他临床特征，包括遗传综合征。常染色体显性变异的 TAB2 被美国心脏协会认为是导致非综合征性 CHD 的原因，然而，新出现的数据表明 TAB2 变异与额外的心脏外特征有关。我们确定了 15 名新报告的具有致病性 TAB2 变异的个体，并在文献中回顾了另外 24 名具有 TAB2 变异的个体。分析表明，64%（25/39）因 TAB2 单核苷酸变异（SNV）而患病的个体具有综合征性 CHD 或成年起病的心肌病，并有一个或多个心脏外特征。最常与 CHD 或心肌病共同出现的特征是面部畸形、骨骼和结缔组织缺陷，大多数具有 TAB2 变异的个体表现为结缔组织疾病。值得注意的是，我们队列中的 53%（8/15）显示出发育迟缓，我们怀疑这可能是 TAB2 疾病以前未被认识到的特征。我们描述了最大的 TAB2 SNV 患者队列，并表明除了心脏病外，大多数 TAB2 病例还存在多个系统的特征。鉴于我们的发现，我们建议将 TAB2 列入导致综合征性 CHD、成年起病的心肌病和结缔组织疾病的基因列表中。
