Unité de Génétique Chromosomique, Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France.
Cytometry Core Facility, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
BMC Med Genomics. 2019 Aug 2;12(1):116. doi: 10.1186/s12920-019-0558-8.
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.
平衡结构变体大多在具有基因缺失或断裂点细微重排的疾病中描述。
这里我们报告了一例轻度智力缺陷患者，携带新发平衡易位 t(3;5)。通过微阵列、Array Painting 和 Sanger 测序全面探索了断裂点。未发现基因缺失，但染色体 5 的断裂点定位于 MEF2C 基因上游 228-kb。预测的拓扑关联域分析表明，它仅包含 MEF2C 基因和长非编码 RNA LINC01226。寻找 MEF2C 基因表达的 RNA 研究显示，患者的淋巴母细胞系中 MEF2C 过度表达。
MEF2C 过度表达的致病性尚不清楚，因为文献中仅描述了四名携带包含 MEF2C 的 5q14.3 微重复的轻度智力缺陷患者。这些个体中的微重复还包含其他在大脑中表达的基因。该患者表现出与 5q14.3 微重复患者相同的表型。我们报告了首例导致 MEF2C 过度表达的平衡易位，类似于功能性重复。
