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Abstract：
Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with CRD included intellectual disability/developmental delay (91%) with speech delay (65%), motor delay (53%), feeding difficulties/failure to thrive (66%), ocular abnormalities (56%), musculoskeletal anomalies (53%), and behavioral problems (52%). Other congenital anomalies were also reported, but none of them were common. Our findings expanded the genotypic and phenotypic spectrum of CRD that will guide genetic counseling, management, and surveillance care for patients with CRD. Additionally, a newly built facial gestalt on the Face2Gene tool will facilitate prompt recognition of CRD by physicians and shorten a patient\'s diagnostic odyssey.
摘要：
CTCF的单等位基因变异导致具有广泛特征的常染色体显性神经发育障碍。包括对大脑的影响，增长,和颅面发育。由于外显子组测序的应用增加，已经确定了越来越多的CTCF相关疾病（CRD）受试者。需要进一步描述CRD的临床谱。这里,我们检查了临床特征，包括面部轮廓,和107名具有确定的CTCF变体的受试者的基因型谱，包括43个新的和64个先前描述的主题。在43个新学科中，报告了23种新的变体。CRD患者的主要临床特征包括智力障碍/发育迟缓（91％）和言语迟缓（65％），电机延迟（53%），喂养困难/未能茁壮成长(66%)，眼部异常（56%），肌肉骨骼异常（53%），和行为问题（52%）。还报告了其他先天性异常，但它们都不常见。我们的发现扩展了CRD的基因型和表型谱，这将指导遗传咨询，管理,和对CRD患者的监测护理。此外,Face2Gene工具上新建的面部完形将有助于医生及时识别CRD，并缩短患者的诊断冒险之旅。
