Faculty of Medicine, Department of Medical Genetics, Hacettepe University, Ankara, Turkey.
Department of Medical Genetics, Ankara Ataturk Training and Research Hospital, Yildirim Beyazit University, Ankara, Turkey.
J Intellect Disabil Res. 2019 Jun;63(6):548-557. doi: 10.1111/jir.12592. Epub 2019 Feb 18.
Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings.
Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1-6 in RBM8A.
Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889-kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12).
Although the deletion in case 5 did not include the thrombocytopenia-absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia-absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype-phenotype correlations for this region.
1 号染色体 1q21 区域的重排表现为多种表型，包括小头畸形、智力障碍、面部畸形、眼部异常、心脏缺陷、泌尿生殖系统异常、自闭症谱系障碍、精神疾病和癫痫发作。在此，我们描述了 8 例 1q21 缺失和重复综合征患者，并发现了新的缺失和发现。
采用染色体微阵列分析来确定拷贝数变异的存在。使用针对 1 号染色体 1q21 区域的特异性引物进行定量聚合酶链反应。对 5 号病例进行 RBM8A 外显子 1-6 的直接基因组测序进行突变分析。
拷贝数变异分析在 8 例患者中发现了 1q21 区域的 7 个缺失和 1 个重复。此外，4 个变异是新生的，其中 2 个缺失是首次报道。其中一个病例（病例 7）表现为中度智力障碍和面部畸形，而染色体微阵列分析显示病例 7在 1q21 近端区域（GPR89A、PDZK1、CD160、POLR3C 和 NBPF12）存在 889kb 的缺失。
虽然 5 号病例的缺失不包括血小板减少-桡骨缺失综合征关键区域或 RBM8A 基因，但他存在胸肌发育不良、桡骨和肱骨发育不良以及短弯曲肋骨，这表明可能存在血小板减少-桡骨缺失区域修饰因子。7 号病例的发现表明 1q21 微缺失综合征区域的近端部分对于临床症状的发生可能非常重要。在提出的病例中观察到了一些新的发现，例如桡骨和肱骨发育不良和脑干发育不良。提出的发现扩展了 1q21 异常的谱，并为该区域的基因型-表型相关性提供了证据。
