Abstract：
Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62 Mb minimal critical region at 20q11.2, encompassing three genes GDF5, EPB41L1, and SAMHD1, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359 kb at 20q11.2, containing six MIM genes, including two disease-causing genes, GDF5 and CEP250. The second critical region spans 706 kb at 20q12, encompassing four MIM genes, including two disease-causing genes, MAFB and TOP1. We propose GDF5 to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize TOP1 as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.
摘要：
20号染色体（20q）长臂的缺失很少见，只有16例报告的患者显示近端间质20q缺失。在20q11.2处的1.62Mb最小临界区域，包括三个基因GDF5，EPB41L1和SAMHD1，被认为是该综合征的原因。主要的临床特征包括生长迟缓，顽固性进食困难与胃食管反流，张力减退和精神运动性发育迟缓。常见的面部畸形，包括三角脸，超端粒,此外还报告了发育不良的鼻翼。这里,我们介绍了5例近侧间质20q缺失的新患者的临床和分子研究结果。我们分析了所有先前报道的20q11.2q12微缺失患者的表型和分子数据，还有我们的五个新案子.我们队列中患者的拷贝数变异分析使我们能够识别20q11.2q12区域中的第二个关键区域，并重新定义最初识别的第一个区域。第一个关键区域在20q11.2处跨越359kb，包含六个MIM基因，包括两个致病基因，GDF5和CEP250。第二个关键区域在20q12跨越706kb，包含四个MIM基因，包括两个致病基因，MAFB和TOP1。我们建议GDF5是产生20q11.2缺失患者表型的主要候选基因。此外，我们假设TOP1是20q12第二个关键区域的潜在候选基因。值得注意的是，我们不能排除参与缺失的其他基因的协同作用的可能性，包括影响两个关键区域的连续基因缺失综合征或位置效应。需要针对近端20q缺失患者的进一步研究来支持我们的假设。
