Terminal microdeletions of the long arm of chromosome 6 are associated with a phenotype that includes multiple brain malformations, intellectual disability, and epilepsy. A 1.7-Mb region has been proposed to contain a gene responsible for the brain anomalies. Here, we present the case of a 12-year-old girl with multiple brain alterations and moderate intellectual disability with a 18-kb deletion in chromosome 6q27, which is smaller than the microdeletions previously described by microarray analysis. We refined the smallest region of overlap possibly associated with the phenotype of brain malformations and intellectual disability to a segment of 325 kb, comprising the DLL1, PSMB1, TBP, and PDCD2 genes since these genes were structurally and/or functionally lost in the smaller deletions described to date. We hypothesize that DLL1 is responsible for brain malformations and possibly interacts with other adjacent genes. The TBP gene encodes a transcription factor which is potentially related to cognitive development. TBP is linked to PSMB1 and PDCD2 in a conserved manner among mammals, suggesting a potential interaction between these genes. In conclusion, the 6q27 microdeletion is a complex syndrome with variable expressivity of brain malformations and intellectual disability phenotypes which are possibly triggered by the 4 genes described and adjacent genes susceptible to gene regulation changes.

中文翻译：

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在6q27微缺失中定义智力障碍和脑畸形的关键区域。

6号染色体长臂的末端微缺失与一种表型有关，该表型包括多种脑畸形，智力障碍和癫痫病。已经提出了一个1.7 Mb的区域，该区域包含负责大脑异常的基因。在这里，我们提出了一个12岁女孩的案例，该女孩具有多个脑部改变和中度智力障碍，在6q27染色体上缺失了18kb，比以前通过微阵列分析描述的微缺失小。我们将可能与脑畸形和智力障碍表型有关的最小重叠区域细化为325 kb的片段，其中包括DLL1，PSMB1，TBP和PDCD2基因，因为这些基因在较小的缺失中在结构和/或功能上丧失了迄今为止描述。我们假设DLL1负责脑畸形，并可能与其他邻近基因相互作用。TBP基因编码可能与认知发展有关的转录因子。TBP在哺乳动物中以保守的方式与PSMB1和PDCD2连接，表明这些基因之间存在潜在的相互作用。总之，6q27微缺失是一种复杂的综合症，具有大脑畸形和智力残疾表型的可变表达能力，这可能是由所述的4个基因和邻近基因易受基因调控变化触发的。说明这些基因之间可能存在相互作用。总之，6q27微缺失是一种复杂的综合症，具有大脑畸形和智力残疾表型的可变表达能力，这可能是由所述的4个基因和邻近基因易受基因调控变化触发的。表明这些基因之间可能存在相互作用。总之，6q27微缺失是一种复杂的综合症，具有大脑畸形和智力残疾表型的可变表达能力，这可能是由所述的4个基因和邻近基因易受基因调控变化触发的。