Abstract：
Coffin-Siris syndrome (CSS) is a neurodevelopmental disorder characterized by cognitive disability, coarse facial features, hypertrichosis, and somatic dysmorphic features. It is caused by mutations in the BAF-complex or SOX gene. Here, a Chinese woman presenting with neurodevelopmental delay, mild intellectual disability, speech delay, dysmorphic features, obesity, scoliosis, hypotonia, seizures, skin problems, hypokalemia, and endocrine dysfunction is described. Whole exome sequencing (WES) identified a heterozygous missense variant, c.2074G > C (p. Ala692Pro), in the SMARCC2 gene of the proband. Affecting chromatin structure, SMARCC2 plays an essential role in modulating cortical neurogenesis, and controlling cortical size and thickness. Moreover, it is associated with tumor suppression, and SMARCC2 mutations have been observed with high frequency in human cancers. While this is the second report of SMARCC2 mutations in patients with detailed phenotypes, this is the first describing the observation of electrolyte disturbances and endocrinopathy. These findings expanded the genetic and clinical spectrum of SMARCC2-related Coffin-Siris syndrome.
摘要：
Coffin-Siris综合征（CSS）是一种以认知障碍为特征的神经发育障碍，粗糙的面部特征，多毛症,和躯体畸形特征。它是由BAF复合物或SOX基因突变引起的。这里,一位患有神经发育迟缓的中国女性，轻度智力残疾,说话延迟,变形特征，肥胖，脊柱侧弯,低张力,癫痫发作,皮肤问题,低钾血症,描述了内分泌功能障碍。全外显子组测序（WES）确定了一个杂合错义变异，c.2074G>C（p。Ala692Pro),在先证者的SMARCC2基因中。影响染色质结构，SMARCC2在调节皮质神经发生中起重要作用，控制皮质的大小和厚度.此外，它与肿瘤抑制有关，在人类癌症中观察到SMARCC2突变的频率很高。虽然这是第二次报告SMARCC2突变的患者详细的表型，这是第一次描述电解质紊乱和内分泌疾病的观察。这些发现扩大了SMARCC2相关Coffin-Siris综合征的遗传和临床范围。
