While chromosome 1p36 deletion syndrome is one of the most common terminal subtelomeric microdeletion syndrome, 1p36 microduplications are rare events. Polymicrogyria (PMG) is a brain malformation phenotype frequently present in patients with 1p36 monosomy. The gene whose haploinsufficiency could cause this phenotype remains to be identified. We used high-resolution arrayCGH in patients with various forms of PMG in order to identify chromosomal variants associated to the malformation and characterized the genes included in these regions in vitro and in vivo. We identified the smallest case of 1p36 duplication reported to date in a patient presenting intellectual disability, microcephaly, epilepsy, and perisylvian polymicrogyria. The duplicated segment is intrachromosomal, duplicated in mirror and contains two genes: enolase 1 (ENO1) and RERE, both disrupted by the rearrangement. Gene expression analysis performed using the patient cells revealed a reduced expression, mimicking haploinsufficiency. We performed in situ hybridization to describe the developmental expression profile of the two genes in mouse development. In addition, we used in utero electroporation of shRNAs to show that Eno1 inactivation in the rat causes a brain development defect. These experiments allowed us to define the ENO1 gene as the most likely candidate to contribute to the brain malformation phenotype of the studied patient and consequently a candidate to contribute to the malformations of the cerebral cortex observed in patients with 1p36 monosomy.

虽然染色体 1p36 缺失综合征是最常见的末端亚端粒微缺失综合征之一，但 1p36 微重复是罕见的事件。多小脑回 (PMG) 是一种常见于 1p36 单体患者的脑畸形表型。单倍体不足可能导致这种表型的基因仍有待确定。我们在各种形式的 PMG 患者中使用了高分辨率 arrayCGH，以识别与畸形相关的染色体变异，并在体外和体内表征这些区域中包含的基因。我们确定了迄今为止报告的最小的 1p36 重复病例，该病例出现在一名患有智力障碍、小头畸形、癫痫和侧裂周围多小脑回的患者中。复制片段在染色体内，镜像复制并包含两个基因：烯醇化酶 1 (ENO1 ) 和RERE，都被重排打乱了。使用患者细胞进行的基因表达分析显示表达降低，模拟单倍剂量不足。我们进行了原位杂交来描述这两个基因在小鼠发育中的发育表达谱。此外，我们在子宫内使用shRNA 电穿孔来证明大鼠中的Eno1失活会导致大脑发育缺陷。这些实验使我们能够将ENO1基因定义为最有可能导致所研究患者的脑畸形表型的候选基因，因此也是导致 1p36 单体患者中观察到的大脑皮层畸形的候选基因。