Microarray-based comparative genomic hybridization (aCGH) is being increasingly applied to delineate novel genomic disorders and related syndromes in patients with developmental delay. In this study, detailed clinical and cytogenetic data of three unrelated patients with interstitial 2q12.3q13 microdeletion were described and compared with thirteen 2q12.3q13 microdeletion patients, gathered from the medical literature and public databases. 60 K aCGH analysis revealed three overlapping 2q12.3q13 microdeletions measuring 1.88 Mb in patient 1, 1.25 Mb in patient 2, and 0.41 Mb in patient 3, respectively. Confirmation and segregation studies were performed using fluorescence in situ hybridization (FISH) and quantitative real-time PCR. Variable clinical features of 2q12.3q13 microdeletion including microcephaly, prenatal growth retardation, developmental delay, short stature, behavioral problems, learning difficulties, skeletal anomalies, congenital heart defects, and features of ectodermal dysplasia were observed. The boundaries and sizes of the 2q12.3q13 deletions in the sixteen patients were different, but an overlapping region of 249 kb in 2q12.3 was defined. The SRO (smallest region of overlap) encompasses four genes, including LIMS1, RANBP2, CCDC138, and EDAR. Among these genes, RANBP2 is a strong candidate gene for neurological phenotype and genetic susceptibility to viral infections. To our knowledge, this is the first published report of 2q12.3q13 microdeletion syndrome and our observations strongly suggest that these recurrent CNVs may be a novel risk factor for developmental delay with variable expressivity and incomplete penetrance.

基于微阵列的比较基因组杂交 (aCGH) 越来越多地应用于描述发育迟缓患者的新型基因组疾病和相关综合征。在这项研究中，描述了三名不相关的间质 2q12.3q13 微缺失患者的详细临床和细胞遗传学数据，并与从医学文献和公共数据库收集的 13 名 2q12.3q13 微缺失患者进行了比较。60 K aCGH 分析显示三个重叠的 2q12.3q13 微缺失分别在患者 1 中测量为 1.88 Mb、在患者 2 中测量为 1.25 Mb 在患者 3 中测量为 0.41 Mb。使用荧光原位杂交 (FISH) 和定量实时 PCR 进行确认和分离研究。2q12.3q13 微缺失的可变临床特征包括小头畸形、产前生长迟缓、观察到发育迟缓、身材矮小、行为问题、学习困难、骨骼异常、先天性心脏缺陷和外胚层发育不良的特征。16 例患者 2q12.3q13 缺失的边界和大小不同，但在 2q12.3 中定义了 249 kb 的重叠区域。SRO（最小重叠区域）包含四个基因，包括LIMS1、RANBP2、CCDC138和EDAR。在这些基因中，RANBP2是神经表型和病毒感染遗传易感性的强候选基因。据我们所知，这是第一份发表的关于 2q12.3q13 微缺失综合征的报告，我们的观察强烈表明这些复发性 CNV 可能是发育迟缓的新风险因素，具有可变的表达性和不完全的外显率。