BACKGROUND The clinical features of Down syndrome vary among individuals, with those most common being congenital heart disease, intellectual disability, developmental abnormity and dysmorphic features. Complex combination of Down syndrome phenotype could be produced by partially copy number variations (CNVs) on chromosome 21 as well. By comparing individual with partial CNVs of chromosome 21 with other patients of known CNVs and clinical phenotypes, we hope to provide a better understanding of the genotype-phenotype correlation of chromosome 21. METHODS A total of 2768 pediatric patients sample collected at the Genetics Laboratory at Oklahoma University Health Science Center were screened using CGH Microarray for CNVs on chromosome 21. RESULTS We report comprehensive clinical and molecular descriptions of six patients with microduplication and seven patients with microdeletion on the long arm of chromosome 21. Patients with microduplication have varied clinical features including developmental delay, microcephaly, facial dysmorphic features, pulmonary stenosis, autism, preauricular skin tag, eye pterygium, speech delay and pain insensitivity. We found that patients with microdeletion presented with developmental delay, microcephaly, intrauterine fetal demise, epilepsia partialis continua, congenital coronary anomaly and seizures. CONCLUSION Three patients from our study combine with four patients in public database suggests an association between 21q21.1 microduplication of CXADR gene and patients with developmental delay. One patient with 21q22.13 microdeletion of DYRK1A shows association with microcephaly and scoliosis. Our findings helped pinpoint critical genes in the genotype-phenotype association with a high resolution of 0.1 Mb and expanded the clinical features observed in patients with CNVs on the long arm of chromosome 21.

中文翻译：

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在先天性异常患者中通过比较基因组杂交 (CGH) 微阵列检测 21 号染色体上的拷贝数变异研究。

背景唐氏综合症的临床特征因人而异，最常见的是先天性心脏病、智力障碍、发育异常和畸形特征。唐氏综合征表型的复杂组合也可以由 21 号染色体上的部分拷贝数变异 (CNV) 产生。通过比较具有 21 号染色体部分 CNV 的个体与其他已知 CNV 和临床表型的患者，我们希望更好地了解 21 号染色体的基因型-表型相关性。俄克拉荷马大学健康科学中心使用 CGH 微阵列筛选 21 号染色体上的 CNV。结果 我们报告了 6 例微重复患者和 7 例 21 号染色体长臂微缺失患者的全面临床和分子描述。微重复患者具有不同的临床特征，包括发育迟缓、小头畸形、面部畸形特征、肺动脉狭窄、自闭症、耳前皮肤标签，眼翼状胬肉，言语延迟和疼痛不敏感。我们发现微缺失患者出现发育迟缓、小头畸形、胎儿宫内死亡、持续偏瘫、先天性冠状动脉异常和癫痫发作。结论 我们研究中的三名患者与公共数据库中的四名患者相结合，表明 CXADR 基因的 21q21.1 微复制与发育迟缓患者之间存在关联。一名患有 21q22 的患者。13 DYRK1A 的微缺失显示与小头畸形和脊柱侧凸相关。我们的研究结果有助于以 0.1 Mb 的高分辨率确定基因型-表型关联中的关键基因，并扩展在 21 号染色体长臂上的 CNV 患者中观察到的临床特征。