Further delineation of the SATB2 phenotype
Further delineation of the SATB2 phenotype
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DOI：
10.1038/ejhg.2013.280
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发表时间：
2014-08-01
影响因子：
5.2
通讯作者：
Bartholdi, Deborah
中科院分区：
文献类型：
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作者：
Doecker, Dennis;Schubach, Max;Bartholdi, Deborah
SATB2是一个进化上高度保守的染色质重塑基因，位于染色体2q33.1上。脊椎动物模型表明，Satb2在颅面图案和成骨细胞分化以及决定发育中的新皮层中神经元投射的命运中起着至关重要的作用。在人类中，2q33.1染色体易位和缺失导致SATB2单倍不全与腭裂（CP）、面部畸形和智力残疾（ID）有关。迄今为止，仅报道了一例携带SATB2无义突变的患者。在这项研究中，我们对一名患有CP和严重语言发育迟缓的3岁女孩及其未受影响的父母进行了三外显子组测序。此前，该女孩接受了常规和分子核型分析（微阵列分析），以及与发育迟缓相关的不同疾病的靶向分析，包括Angelman综合征、Rett综合征和脆性X综合征。无法确诊。外显子组测序显示在SATB2基因（c.715C > T; p.R239*）中有一个从头无义突变。第二例携带SATB2从头无义突变的患者的鉴定证实，该基因对正常颅面模式和认知发育至关重要。根据我们的数据和迄今为止发表的文献，我们提出了一种新的临床可识别的综合征- satb2相关综合征（SAS）。SAS可能未被充分诊断，在患有ID、严重语言延迟、腭裂或高弓腭、牙列异常、牙齿拥挤和形状不规则的儿童中应予以考虑。
SATB2 is an evolutionarily highly conserved chromatin remodeling gene located on chromosome 2q33.1. Vertebrate animal models have shown that Satb2 has a crucial role in craniofacial patterning and osteoblast differentiation, as well as in determining the fates of neuronal projections in the developing neocortex. In humans, chromosomal translocations and deletions of 2q33.1 leading to SATB2 haploinsufficiency are associated with cleft palate (CP), facial dysmorphism and intellectual disability (ID). A single patient carrying a nonsense mutation in SATB2 has been described to date. In this study, we performed trio-exome sequencing in a 3-year-old girl with CP and severely delayed speech development, and her unaffected parents. Previously, the girl had undergone conventional and molecular karyotyping (microarray analysis), as well as targeted analysis for different diseases associated with developmental delay, including Angelman syndrome, Rett syndrome and Fragile X syndrome. No diagnosis could be established. Exome sequencing revealed a de novo nonsense mutation in the SATB2 gene (c.715C > T; p.R239*). The identification of a second patient carrying a de novo nonsense mutation in SATB2 confirms that this gene is essential for normal craniofacial patterning and cognitive development. Based on our data and the literature published so far, we propose a new clinically recognizable syndrome - the SATB2-associated syndrome (SAS). SAS is likely to be underdiagnosed and should be considered in children with ID, severe speech delay, cleft or high-arched palate and abnormal dentition with crowded and irregularly shaped teeth.