The nuclear factor one (NFI) site-specific DNA-binding proteins represent a family of transcription factors that are important for the development of multiple organ systems, including the brain. During brain development in mice, the expression patterns of Nfia, Nfib, and Nfix overlap, and knockout mice for each of these exhibit overlapping brain defects, including megalencephaly, dysgenesis of the corpus callosum, and enlarged ventricles, which implies a common but not redundant function in brain development. In line with these models, human phenotypes caused by haploinsufficiency of NFIA, NFIB, and NFIX display significant overlap, sharing neurodevelopmental deficits, macrocephaly, brain anomalies, and variable somatic overgrowth. Other anomalies may be present depending on the NFI gene involved. The possibility of variants in NFI genes should therefore be considered in individuals with intellectual disability and brain overgrowth, with individual NFI-related conditions being differentiated from one another by additional signs and symptoms. The exception is provided by specific NFIX variants that act in a dominant negative manner, as these cause a recognizable entity with more severe cognitive impairment and marked bone dysplasia, Marshall-Smith syndrome. NFIX duplications are associated with a phenotype opposite to that of haploinsufficiency, characterized by short stature, small head circumference, and delayed bone age. The spectrum of NFI-related disorders will likely be further expanded, as larger cohorts are assessed.

中文翻译：

---

核因子I基因的变异影响生长和发育。

核因子一（NFI）位点特异性DNA结合蛋白代表一系列转录因子，这些因子对包括大脑在内的多种器官系统的发育都很重要。在小鼠的大脑发育过程中，Nfia，Nfib和Nfix的表达模式重叠，并且每种基因敲除小鼠均表现出重叠的大脑缺陷，包括巨头畸形，gene体发育不全和脑室扩大，这意味着常见但并非多余在大脑发育中起作用。与这些模型一致，由NFIA，NFIB和NFIX的单倍不足引起的人类表型表现出明显的重叠，共享神经发育缺陷，大头畸形，脑部异常和体细胞过度生长。根据涉及的NFI基因，可能会出现其他异常情况。因此，应在智力障碍和大脑过度发育的个体中考虑NFI基因变异的可能性，并通过其他体征和症状将个体与NFI相关的疾病区分开。特定的NFIX变体提供了例外，这些变体以显性负性方式发挥作用，因为这些变体导致可识别的实体出现更严重的认知障碍和明显的骨发育异常，即Marshall-Smith综合征。NFIX重复与单倍体功能不全的表型有关，其特征是身材矮小，头围小和骨龄延迟。随着对更大人群的评估，与NFI相关的疾病的范围可能会进一步扩大。与NFI相关的个体病因其他体征和症状而有所不同。特定的NFIX变体提供了例外，这些变体以显性负性方式发挥作用，因为这些变体导致可识别的实体出现更严重的认知障碍和明显的骨发育异常，即Marshall-Smith综合征。NFIX重复与单倍体功能不全的表型有关，其特征是身材矮小，头围小和骨龄延迟。随着对更大人群的评估，与NFI相关的疾病的范围可能会进一步扩大。与NFI相关的个体病因其他体征和症状而有所不同。特定的NFIX变体提供了例外，这些变体以显性负性方式发挥作用，因为这些变体导致可识别的实体出现更严重的认知障碍和明显的骨发育异常，即Marshall-Smith综合征。NFIX重复与单倍体功能不全的表型有关，其特征是身材矮小，头围小和骨龄延迟。随着对更大人群的评估，与NFI相关的疾病的范围可能会进一步扩大。因为这些会导致可识别的实体出现更严重的认知障碍和明显的骨发育不良，即Marshall-Smith综合征。NFIX重复与单倍体功能不全的表型有关，其特征是身材矮小，头围小和骨龄延迟。随着对更大人群的评估，与NFI相关的疾病的范围可能会进一步扩大。因为这些会导致可识别的实体出现更严重的认知障碍和明显的骨发育不良，即马歇尔-史密斯综合征。NFIX重复与单倍体功能不全的表型有关，其特征是身材矮小，头围小和骨龄延迟。随着对更大人群的评估，与NFI相关的疾病的范围可能会进一步扩大。