Coutton Charles, Dieterich Klaus, Satre Véronique, Vieville Gaëlle, Amblard Florence, David Marie, Cans Christine, Jouk Pierre-Simon, Devillard Francoise
Laboratoire de Génétique Chromosomique, Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble, 38700, Grenoble, France,
Eur J Pediatr. 2015 Jan;174(1):75-83. doi: 10.1007/s00431-014-2367-6. Epub 2014 Jul 3.
Intellectual disability (ID) is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of ID originate from chromosomal imbalances. During the last years, array-CGH has successfully contributed to improve the diagnostic detection rate of genetic abnormalities in patients with ID. Most array-CGH studies focused on patients with moderate or severe intellectual disability. Studies on genetic etiology in children with mild intellectual disability (ID) are very rare. We performed array-CGH analysis in 66 children with mild intellectual disability assessed in a population-based study and for whom no genetic etiology was identified. We found one or more copy number variations (CNVs) in 20 out of 66 (30 %) patients with a mild ID. In eight of them (12 %), the CNVs were certainly responsible for the phenotype and in six they were potentially pathogenic for ID. Altogether, array-CGH helped to determine the etiology of ID in 14 patients (~21 %).
Our results underscore the clinical relevance of array-CGH to investigate the etiology of isolated idiopathic mild ID in patients or associated with even subtle dysmorphic features or congenital malformations.
智力残疾（ID）的特征是智力功能和适应性行为受限，起病于儿童期。常见的可识别的ID病因源自染色体失衡。在过去几年中，阵列比较基因组杂交（array-CGH）已成功提高了ID患者遗传异常的诊断检出率。大多数阵列比较基因组杂交研究集中在中度或重度智力残疾患者。关于轻度智力残疾（ID）儿童遗传病因的研究非常罕见。我们对66名在一项基于人群的研究中评估的轻度智力残疾儿童进行了阵列比较基因组杂交分析，这些儿童未发现遗传病因。我们在66名轻度ID患者中的20名（约30%）发现了一个或多个拷贝数变异（CNV）。其中8名（约12%）患者的CNV肯定是导致该表型的原因，6名患者的CNV可能是ID的致病因素。总之，阵列比较基因组杂交有助于确定14名患者（约21%）ID的病因。
我们的结果强调了阵列比较基因组杂交在研究孤立性特发性轻度ID患者或伴有细微畸形特征或先天性畸形患者病因方面的临床相关性。
