Intragenic Duplication-A Novel Causative Mechanism for SATB2-Associated Syndrome
Intragenic Duplication-A Novel Causative Mechanism for SATB2-Associated Syndrome
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DOI：
10.1002/ajmg.a.36769
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发表时间：
2014-12-01
影响因子：
2
通讯作者：
Lundberg, Elisabeth Syk
中科院分区：
文献类型：
--
作者：
Lieden, Agne;Kvarnung, Malin;Lundberg, Elisabeth Syk
先前的研究表明，涉及特殊的富含AT的序列结合蛋白2（SATB 2）基因的遗传畸变导致综合征性智力残疾的可变表型。虽然只有少数患者已被描述，已经有相当大的变化方面的潜在的分子机制，从结构变异跨越点突变。我们在这里描述一个男性病人智力残疾，言语和语言障碍，腭裂，畸形牙齿，和少牙。阵列CGH分析确定了一个小的基因内重复的SATB 2基因，包括三个编码外显子。通过多重连接依赖探针扩增和低覆盖全基因组配对测序证实了结果。WGS断裂点分析直接证实了重复是基因内的。这是第一个报告的患者与基因内重复在SATB 2结合的表型是高度相似的，以前描述的患者与小缺失或点突变的相同基因。我们的研究结果扩展了SATB 2突变的谱，并证实了存在一个独特的SATB 2-表型与严重的ID和语音障碍，腭裂和/或高弓腭，牙齿异常。对于存在这种临床表现的患者，除了SATB 2测序外，还应考虑高分辨率外显子靶向阵列CGH和/或WGS。(c)2014 Wiley Periodicals，Inc.
Previous studies have shown that genetic aberrations involving the special AT-rich sequence-binding protein 2 (SATB2) gene result in a variable phenotype of syndromic intellectual disability. Although only a small number of patients have been described, there is already considerable variation in regard to the underlying molecular mechanism spanning from structural variation to point mutations. We here describe a male patient with intellectual disability, speech and language impairment, cleft palate, malformed teeth, and oligodontia. Array CGH analysis identified a small intragenic duplication in the SATB2 gene that included three coding exons. The result was confirmed by multiplex ligation-dependent probe amplification and low coverage whole genome mate pair sequencing. WGS breakpoint analysis directly confirmed the duplication as intragenic. This is the first reported patient with an intragenic duplication in SATB2 in combination with a phenotype that is highly similar to previously described patients with small deletions or point mutations of the same gene. Our findings expand the spectra of SATB2 mutations and confirm the presence of a distinct SATB2-phenotype with severe ID and speech impairment, cleft palate and/or high arched palate, and abnormalities of the teeth. For patients that present with this clinical picture, a high-resolution exon targeted array CGH and/or WGS, in addition to sequencing of SATB2, should be considered. (c) 2014 Wiley Periodicals, Inc.