Cornelia de Lange syndrome (CdLS), Rubinstein–Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL , SMC1A , SMC3 , HDAC8 , RAD21 , ANKRD11 , and BRD4 , were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300 , have been associated with RSTS, whereas KBG results from variants in ANKRD11 . By exome sequencing, a genetic cause was elucidated in two patients with clinical diagnosis of CdLS but without variants in known CdLS genes. In particular, genetic variants in EP300 and ANKRD11 were identified in the two patients with CdLS. EP300 and ANKRD11 pathogenic variants caused the reduction of the respective proteins suggesting that their low levels contribute to CdLS‐like phenotype. These findings highlight the clinical overlap between CdLS, RSTS, and KBG and support the notion that these rare disorders are linked to abnormal chromatin remodeling, which in turn affects the transcriptional machinery.

中文翻译：

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表型重叠Cornelia de Lange综合征的患者的EP300和ANKRD11病原体变异。

Cornelia de Lange综合征（CdLS），Rubinstein–Taybi综合征（RSTS）和KBG综合征是三种不同的人类发育障碍。变体，属于黏附途径，7个基因NIPBL，SMC1A，SMC3，HDAC8，RAD21，ANKRD11，和BRD4，在患者的CDL的约80％进行了鉴定，这表明更多的致病基因有待发现。RSTS关联了两个基因CREBBP和EP300，而KBG则来自ANKRD11的变体。通过外显子组测序，阐明了两名临床诊断为CdLS但无已知CdLS基因变异的患者的遗传原因。特别是，在两名患有CdLS的患者中鉴定出了EP300和ANKRD11中的遗传变异。EP300和ANKRD11致病性变异导致各自蛋白质的减少，表明它们的低水平有助于CdLS样表型。这些发现凸显了CdLS，RSTS和KBG之间的临床重叠，并支持以下观点：这些罕见疾病与染色质异常重塑有关，进而影响转录机制。