15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: A series of 52 patients
15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: A series of 52 patients
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DOI：
10.1016/j.ejmg.2015.01.002
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发表时间：
2015-03-01
影响因子：
1.9
通讯作者：
Andrieux, Joris
中科院分区：
文献类型：
--
作者：
Vanlerberghe, Clemence;Petit, Florence;Andrieux, Joris
15号染色体长臂的近端区域富含重复子，其定义了15 q重排的五个断点（BP）。BP 1和BP 2之间的15q11.2微缺失与发育迟缓和非典型心理模式有关。该区域包含四个高度保守的非印迹基因：NIPA 1，NIPA 2，CYFIP 1，TUBGCP 5。我们的目标是调查与这种微缺失相关的表型在一个队列的52 patients.This拷贝数变异（CNV）是普遍存在于0.8%的患者表现为发育迟缓，心理模式的问题和/或多种先天性畸形。这是在六个不同的法国遗传实验室通过阵列CGH研究的。我们收集了52名无关患者的数据（包括3个胎儿）排除相关遗传改变的患者后在52名患者中，68.3%观察到轻度或中度发育迟缓，85.4%有语言障碍，63.4%有心理问题，如注意力缺陷和多动障碍，自闭症谱系障碍或强迫症。18.7%的患者出现癫痫发作，17.3%的患者出现相关先天性心脏病。在65.4%的家庭中，父母被分析为该地区的异常。在这些家庭中，18.8%观察到“从头”微缺失，81.2%是从父母之一遗传的。我们的研究结果支持了15q11.2（BP 1-BP 2）微缺失与发育迟缓、行为异常、全身性癫痫和先天性心脏病相关的假说。后一个特征很少被描述。表达的不完全性和变异性需要进一步的评估和研究。(C)2015年由Elsevier Masson SAS出版。
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. (C) 2015 Published by Elsevier Masson SAS.