Abstract：
Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and BP2 has been previously associated with developmental delay and atypical psychological patterns. This region contains four highly-conserved and non-imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the phenotypes associated with this microdeletion in a cohort of 52 patients. This copy number variation (CNV) was prevalent in 0.8% patients presenting with developmental delay, psychological pattern issues and/or multiple congenital malformations. This was studied by array-CGH at six different French Genetic laboratories. We collected data from 52 unrelated patients (including 3 foetuses) after excluding patients with an associated genetic alteration (known CNV, aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4% had psychological issues such as Attention Deficit and Hyperactivity Disorder, Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted in 18.7% patients and associated congenital heart disease in 17.3%. Parents were analysed for abnormalities in the region in 65.4% families. Amongst these families, \'de novo\' microdeletions were observed in 18.8% and 81.2% were inherited from one of the parents. Incomplete penetrance and variable expressivity were observed amongst the patients. Our results support the hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The later feature has been rarely described. Incomplete penetrance and variability of expression demands further assessment and studies.
摘要：
15号染色体长臂的近端区域富含重复子，为15q重排定义五个断点(BP)。BP1和BP2之间的15q11.2微缺失先前与发育延迟和非典型心理模式有关。该区域包含四个高度保守且非印迹的基因:NIPA1、NIPA2、CYFIP1、TUBGCP5。我们的目标是在52例患者的队列中研究与这种微缺失相关的表型。这种拷贝数变异（CNV）在0.8％的发育迟缓患者中普遍存在，心理模式问题和/或多种先天性畸形。这是由array-CGH在六个不同的法国遗传实验室进行的研究。我们收集了52例无关患者（包括3个胎儿）的数据，排除了相关遗传改变的患者（已知CNV，非整倍体或已知的单基因疾病)。在52名患者中，在68.3%中观察到轻度或中度发育迟缓,85.4%有言语障碍,63.4%有注意缺陷,多动症等心理问题,自闭症谱系障碍或强迫症。18.7％的患者出现癫痫发作，17.3％的患者出现相关的先天性心脏病。对该地区65.4％家庭的父母进行了异常分析。在这些家庭中，“从头”微缺失在18.8％和81.2％是从父母之一继承的。在患者中观察到不完全的外显率和可变的表达能力。我们的结果支持以下假设：15q11.2（BP1-BP2）微缺失与发育延迟有关，异常行为,全身性癫痫和先天性心脏病。后来的功能很少被描述。不完整的外显率和表达的可变性需要进一步评估和研究。
