TATA-binding protein associated factor 4 (TAF4) is a subunit of the Transcription Factor IID (TFIID) complex, a central player in transcription initiation. Other members of this multimeric complex have been implicated previously as monogenic disease genes in human developmental disorders. TAF4 has not been described to date as a monogenic disease gene. We here present a cohort of eight individuals, each carrying de novo putative loss-of-function (pLoF) variants in TAF4 and expressing phenotypes consistent with a neuro-developmental disorder (NDD). Common features include intellectual disability, abnormal behavior, and facial dysmorphisms. We propose TAF4 as a novel dominant disease gene for NDD, and coin this novel disorder “TAF4-related NDD” (T4NDD). We place T4NDD in the context of other disorders related to TFIID subunits, revealing shared features of T4NDD with other TAF-opathies.

中文翻译：

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TAF4 从头推定的功能丧失变异与神经发育障碍有关

TATA 结合蛋白相关因子 4 (TAF4) 是转录因子 IID (TFIID) 复合体的一个亚基，是转录起始的核心参与者。这种多聚体复合体的其他成员以前曾被认为是人类发育障碍中的单基因疾病基因。迄今为止，TAF4尚未被描述为单基因疾病基因。我们在这里展示了一个由八个人组成的队列，每个人都携带TAF4中的新推定功能丧失 (pLoF) 变异，并表达与神经发育障碍 (NDD) 一致的表型。常见特征包括智力障碍、行为异常和面部畸形。我们提出TAF4作为 NDD 的新型显性疾病基因，并将这种新型疾病命名为“TAF4 相关 NDD”（T4NDD）。我们将 T4NDD 置于与 TFIID 亚基相关的其他疾病的背景下，揭示 T4NDD 与其他 TAF 病症的共同特征。