平衡的结构变体主要在具有基因破坏或断点处的细微重排的疾病中描述。
在这里,我们报告了一名患有轻度智力缺陷的患者,该患者具有从头平衡易位t(3;5)。通过微阵列充分探索了断点,阵列绘画和Sanger测序。未发现基因破坏,但5号染色体断裂点位于MEF2C基因上游228kb。预测的拓扑关联域分析显示其仅包含MEF2C基因和长非编码RNALINC01226。寻找MEF2C基因表达的RNA研究揭示了MEF2C在患者的类淋巴母细胞细胞系中的过表达。
MEF2C过表达的致病性仍不清楚,因为文献中仅描述了4名患有轻度智力缺陷的患者携带含有MEF2C的5q14.3微重复。这些个体中的微重复还包含在大脑中表达的其他基因。该患者表现出与5q14.3微重复患者相同的表型。我们报告了第一例平衡易位导致MEF2C过表达的情况,类似于功能性重复。
Balanced structural variants are mostly described in disease with gene disruption or subtle rearrangement at breakpoints.
Here we report a patient with mild intellectual deficiency who carries a de novo balanced translocation t(3;5). Breakpoints were fully explored by microarray, Array Painting and Sanger sequencing. No gene disruption was found but the chromosome 5 breakpoint was localized 228-kb upstream of the
MEF2C gene. The predicted Topologically Associated Domains analysis shows that it contains only the
MEF2C gene and a long non-coding RNA LINC01226. RNA studies looking for
MEF2C gene expression revealed an overexpression of
MEF2C in the lymphoblastoid cell line of the patient.
Pathogenicity of MEF2C overexpression is still unclear as only four patients with mild intellectual deficiency carrying 5q14.3 microduplications containing
MEF2C are described in the literature. The microduplications in these individuals also contain other genes expressed in the brain. The patient presented the same phenotype as 5q14.3 microduplication patients. We report the first
case of a balanced translocation leading to an overexpression of
MEF2C similar to a functional duplication.