Tatton-Brown-Rahman 综合征是一种罕见的常染色体显性遗传病，由 DNMT3A 基因致病性变异引起，该基因是表观遗传调控的重要参与者，特别是在胚胎发育过程中，在所有组织中高表达。该综合征的主要特征是高生长、大头畸形、智力障碍和面部畸形特征。我们介绍了一个患有 Tatton-Brown-Rahman 综合征的临床病例，该病例是一名患有大头畸形的 10 岁男孩，该男孩患有学习困难、进行性眼部损伤和疲劳，基于深度学习的诊断辅助系统 Face2Gene 怀疑其患有疲劳。先证者接受了全外显子组测序，结果发现 DNMT3A 第 12 外显子中反复出现无义变异，导致杂合子中过早终止密码子 NM_022552.5:c.1443C>A (p.Tyr481Ter) 的形成状态。在父母中没有发现这种变异，证实了它的新生状态。这里描述的患者病例有助于理解塔顿-布朗-拉曼综合征的临床多样性，其轻微的临床表现扩大了该综合征的表型谱。我们报告了 DNMT3A 基因中第一个反复出现的无义变异，表明存在突变热点。该综合征与 Sotos 综合征、Weaver 综合征和 Cowden 综合征的鉴别诊断以及分子确认极为重要，因为 DNMT3A 基因中某些类型致病性变异的存在会显着增加患急性髓系白血病的风险。

Tatton-Brown-Rahman syndrome is a rare autosomal dominant hereditary disease caused by pathogenic variants in the DNMT3A gene, which is an important participant in epigenetic regulation, especially during embryonic development, and is highly expressed in all tissues. The main features of the syndrome are high growth, macrocephaly, intellectual disability, and facial dysmorphic features. We present a clinical case of Tatton-Brown-Rahman syndrome in a ten-year-old boy with macrocephaly with learning difficulties, progressive eye impairment, and fatigue suspected by a deep learning-based diagnosis assistance system, Face2Gene. The proband underwent whole-exome sequencing, which revealed a recurrent nonsense variant in the 12th exon of the DNMT3A, leading to the formation of a premature stop codon-NM_022552.5:c.1443C>A (p.Tyr481Ter), in a heterozygous state. This variant was not found in parents, confirming its de novo status. The patient case described here contributes to the understanding of the clinical diversity of Tatton-Brown-Raman syndrome with a mild clinical presentation that expands the phenotypic spectrum of the syndrome. We report the first recurrent nonsense variant in the DNMT3A gene, suggesting a mutational hot-spot. Differential diagnoses of this syndrome with Sotos syndrome, Weaver syndrome, and Cowden syndrome, as well as molecular confirmation, are extremely important, since the presence of certain types of pathogenic variants in the DNMT3A gene significantly increases the risk of developing acute myeloid leukemia.