De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism.
De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism.
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DOI：
10.1101/mcs.a002097
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发表时间：
2017-11
影响因子：
1.8
通讯作者：
Chung WK
中科院分区：
文献类型：
--
作者：
Tanaka AJ;Cho MT;Willaert R;Retterer K;Zarate YA;Bosanko K;Stefans V;Oishi K;Williamson A;Wilson GN;Basinger A;Barbaro-Dieber T;Ortega L;Sorrentino S;Gabriel MK;Anderson IJ;Sacoto MJG;Schnur RE;Chung WK
使用全外显子组测序，我们确定了7个不相关的个体与全球发展迟缓，肌张力减退，畸形的面部特征，并增加频率的身材矮小，共济失调，自闭症与从头杂合移码，无义，剪接，和错义变异的早期B细胞转录因子家族成员3（EBF 3）基因。EBF 3是collier/olfactory-1/early B-cell factor（COE）蛋白家族的成员，其是中枢神经系统（CNS）发育所需的。COE蛋白在进化上高度保守，在发育过程中调节神经元的特化、迁移、轴突导向和树突发生，并且对于维持成年神经元中的神经元身份是必不可少的。EBF 3的单倍不足可能会影响大脑发育和功能，导致发育迟缓，智力残疾，以及在EBF 3有害变异的个体中观察到的行为差异。
Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 (EBF3) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of EBF3 may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in EBF3.