Bainbridge-Ropers syndrome (BRPS) [OMIM#615485] is a neurodevelopmental disorder, characterized by delayed psychomotor development with generalized hypotonia, intellectual disability with poor or absent speech, feeding difficulties, growth failure, specific craniofacial and minor skeletal features. It was firstly reported in 2013 by Bainbridge et al., who observed a group of individuals sharing overlapping features with Bohring-Opitz syndrome which were caused by pathogenic variant in ASXL1, who indeed carried truncating mutations in ASXL3. To date, 33 cases were described in the literature. BRPS is caused by loss-of-function mutations in ASXL3 which are mostly located in two mutational cluster regions (MCR). The exact molecular mechanism of these mutations resulting in the disease phenotype is still uncertain due to the observation of LOF mutations in healthy population. Here, we report four individuals with BRPS carrying de novo LOF mutations in ASXL3, comparing and summarizing the clinical phenotype of all BRPS reported so far. Furthermore, we try to dissect the genotype-phenotype correlation among the two well reported MCRs in all BRPS from the literature.

Bainbridge-Ropers综合征（BRPS）[OMIM＃615485]是一种神经发育障碍，其特征是精神运动发育迟缓，普遍性肌张力低下，智力低下，言语不佳或缺乏，进食困难，生长衰竭，特定的颅面和骨骼特征。它是由班布里奇（Bainbridge）等人在2013年首次报道的，他观察到一群人具有与Bohring-Opitz综合征相同的重叠特征，这些特征是由ASXL1的致病变异引起的，而这些病原的确在ASXL3中携带了截短的突变。迄今为止，文献中描述了33例。BRPS是由ASXL3中的功能丧失突变引起的它们大多位于两个突变簇区域（MCR）中。由于在健康人群中观察到LOF突变，因此导致疾病表型的这些突变的确切分子机制仍不确定。在这里，我们报告了四名携带ASXL3中从头LOF突变的BRPS的个体，比较并总结了迄今为止报道的所有BRPS的临床表型。此外，我们尝试从文献中剖析所有BRPS中两个报道良好的MCR之间的基因型-表型相关性。